On the Philosophy of New Microbiologys and the Biological Sciences (Jfb)

7/31/2019 On the Philosophy of New Microbiologys and the Biological Sciences (Jfb)

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CENTRE DE LA RECHERCHE SCIENTIFIQUE DU KURDISTAN

C.R.S.K.

Dr Ali KILIC

On the philosophy of “the New Microbiology” and biological Sciences

Paris May 14,

Dedicated to academician Jean François Bach

The Inter Academy symposium was organized by Academy of Sciencesof France by German National Academy of Sciences Leopoldina and by TheRoyal Society in Paris between 14 15 and 16 2012 on the subject The NewMocrobiology. During this symposium, scientists and academics from thesecountries as well as researchers in other states discussed in seven sessionsfundamental we appear very important in terms of division of labor and researchscientists in the field of New Microbiology. This is new and Regulatory SmallRNAs mecanisms and Cellular Microbiology Bacterial Communities MicroniotaSignaling and Cell Biology and Microbial Manipulation of innate and cellular immunity syntetic Genomic and Biology.

The truth is that there is a cart of centuries the biological sciences were the objectconstituting a doctorate in philosophy of science. As was also cited in our projectfor the Foundation of the Academy of Sciences it should be noted this historicaland philosophical academic. There are twenty one years of the century cyncoper in my PhD thesis of my analyzes on the biological sciences that have been one of the principal foundations of the Project for the Foundation of Science AcadéemieKurdistan we have put in evidence the scientific reality of as follows. Before

developing the symposium issue of the New Mocrobiology I would like to paytribute to the academician Jean François Bach.

About our project for the Foundation of the Academy of Sciences academicianJean François Bach responded affirmatively. I received your letter to me bothinterested and excited. with great pleasure that the Academy of Sciences of France and myself, especially, will do everything we can to assist in theestablishment of an Academy of Sciences in Kurdistan. In practice, I send your letter and the folder that accompanies the one hand to the other BréchignacPermanent Secretary Academy currently in charge of international relations and,

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secondly, to Daniel Ricquier Vice President for Relations International.Believe me, dear Dr. Kilic, the assurances of my feelings best. "1

I hereby pay tribute to the academician and dedicated to Jean-François

Bach was elected June 21, 2005 Permanent Secretary of the Academy of Sciences Born June 8, 1940, Jean-François Bach is Professor of Immunology atthe René Descartes University and directs a laboratory at Necker Hospital. Both

physician and researcher, he has remarkably successful synthesis of these twoactivities are mutually enriched throughout his career. He discovered thymulin, athymic hormone ensuring the maturation of T lymphocytes and highlighted therole of regulatory T cells in controlling self-recognition.Passionate about the

pathophysiology of autoimmune diseases, he studied especially the insulin-dependent diabetes that has inspired new therapeutic approaches.

Thus, the work of Jean-François Bach, marked by a highly originalconcept, made him one of the most respected immunologists internationally.Butthe biologist does not stop there and has kept informed on an opening, andsubtle linksmoving between Science and Society. He is particularly involved inthe organization of research and of science education in college.

My research has been developed in the field of immunology. My work was,above all,or experimental procedures in mice, especially in the remarkable

models of spontaneous autoimmune diseases such as lupus NZB mice and NODdiabetic mice. Nevertheless,whenever it has been possible, I was able to transfer the results obtained in animals to human diseases, particularly regarding newimmunotherapy strategies. Of this entanglement between basic research, itsconcepts and techniques, and investigation resulting clinical advances in medicalknowledge. It's Jean Hamburger who impregnated me,at the very beginning of my scientific career, his vision of modern medicalresearch. I had thechance to engage them while the fundamentals of cellular immunology began just to be arrested. The rapid development of this new

discipline has allowed me to surround me, over the four decades of my career, a1Academician Jean François Bach, 3 mai 2012

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significant number of young researchers through which our group was able toestablish and maintain an international presence to this day.1. Discovery of a peptide hormone produced by the thymusWas known since the late 1950s the central role of the thymus in the

differentiation one of two broad categories of lymphocytes, T cells, in particular regarding rejection grafts, defense against viruses and certain bacteria. We knewthat this differentiation dependent interactions between lymphoid precursorsfrom bone marrow and the epithelium thymus. We have demonstrated theexistence of a hormone produced by the thymic epithelium,capable of inducingthe differentiation markers of major T cells on the surface of lymphoid precursors. We isolated this hormone from the blood circulating.Quantities of pure peptide sufficient for sequencing with the techniques of thetime were obtained from several hundred liters of pig's blood. Sequenced in1977 proved to be the hormone peptide of nine amino acids, coupled to zinc.The synthetic hormone stimulates the immune responsesin various models in vitro and in vivo. Its therapeutic activity in humans isdemonstrated in certain immunodeficiencies and in rheumatoid arthritis. Morerecently, and so Unexpectedly, it appeared that some of the hormone and itsanalogues, has potent activity to the extent that these analogues is under development in the pharmaceutical indication.

2. Highlighting the role of regulatory T cells in controlling the recognitionthe self (autoimmunity) It exists in every normal individual autoreactive T cells

recognizing self antigens, specific to the various host tissues. The question aroseas to how this autoreactivity is consistent with the absence of pathological casesoutside of autoimmune disease proved. We were the first to show in early 1980that the main mechanism explaining this paradox is related to the existence of subpopulations of regulatory T cells that oppose the differentiation of

pathogenic T cells responsible for autoimmune diseases. These observations,which were initially obtained in autoimmune diabetes mellitusmice, were at the time against the current dogma that the absence of autoimmunity in healthy individuals could be explained by the elimination or

paralysis of T cells self-reactive pathogens. The concept of immune regulation isnow well established and is the subject of avery large number of basic andapplied research. We continued the characterization phenotypic and functionalregulatory T cells involved in the control of diabetes,gastritis and colitis of autoimmune origin. We have recently shown that, inSurprisingly, distinctsubpopulations of regulatory T cells control the occurrence of thesethree diseases. We have also begun to decipher the genes and moleculesinvolved in these immunoregulatory phenomena.

3. A new treatment for diabetes mellitus can lead to healingdisease Diabetes mellitus is a frequent and severe disorder whose treatment is

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now still only palliative and is based on the chronic administration of insulinfailed to prevent degenerative complications, including vascular disease. Thedemonstration of autoimmune diabetes mellitus should logically lead to try tostop the course of the disease a direct pharmacological action on T cells

involved in its pathogenesis. We realized in 1985 a randomized clinical trialdemonstrating for the first

Once, beyond doubt, the efficacy of immunosuppressive therapy (using thecyclosporine) in patients from a diabetes declare. Complete remissions andsustainable disease were obtained. Unfortunately, the maintenance of remissionrequired continued treatment, which was hardly acceptable in young patients itwas not reasonable exposing the risks of prolonged immunosuppression. Wetherefore decided to seek new methods to restore immune tolerance to self (iecell antigens ß islet insulin-producing). We achieved this goalin 1994 in an experimental model of autoimmune diabetes, NOD mice. Thesimple administration for 5 consecutive days, a monoclonal antibody directedagainst the chain of _CD3 complex bound to the receptor for T-cell recognitionof antigen induced, in therecently become diabetic mice, a permanent remissionof the disease. This remission is intervene for the bulk of regulatory T cells suchas those described above, dependenta cytokine, TGF-ß (transforming growthfactor ß). These spectacular results in the mice led us to develop a treatment

protocol in humans based on same principles. We had, for many, many years, inthe context of organ transplantation, studied the mode of action and side effects

of anti-CD3 antibody, which were the first monoclonal antibodies used inhuman therapy, a few years after the discovery of hybridomas.

The use of anti-CD3 antibodies in autoimmune diseaseswas difficult to implement, because of their strong mitogenic originallysevere side effects associated with a massive release of cytokines. Building onrecent accessibility of an antibody genetically modified non-mitogenic, we wereable to up a randomized trial in 80 diabetic patients from their disease state.

The results this test, which are about to be announced on the occasion of their publication in the New England Journal of Medicine, show that the therapeuticeffect that we described in mice is found in humans. Sixty five percent of

patients treated with anti-CD3 before the autoimmune process has completelydestroyed their beta cells have become insulinoindépendants and are still 18months after treatment for only one week by the antibody.This strategy, which opens, as we had hoped the prospect of a cure of thedisease, should be able to relate to most if not all, of the recent diabetic patientsthe day information for doctors and patients, encouraged by these results, adiagnosis will allow moreearly disease. Experimental and clinical data alsoindicate that this same approach could be extended to other autoimmune

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diseases such as diabetes to multiple sclerosis, to rheumatoid arthritis, Crohn'sdisease and psoriasis.

4. Role of environment in increasing frequency of allergic diseases and

autoimmune in industrialized countriesEpidemiological evidence in recent yearsindicated that the increase in frequencyallergic diseases, including asthma, could be related to the decrease in infections observed for over two decades inindustrialized countries. We have assembled a arguments of epidemiological,clinical and experimental especially confirming this hypothesis and extending tothe autoimmune diseases, in particular insulin-dependent diabetes and multiplesclerosisplates. Experiments in NOD mice have indicated the essential role inthis effect protective infections stimulation of Toll receptors whose key role inimmune responses was first described in Drosophila.

Beyond the explanation that this assumption provides a considerable increase inthe frequency of occurrence allergic diseases and autoimmune diseases, and

possibly some lymphomas and leukemias, these observations open therapeutic perspectives important in providing the hope of substitute for infections"protective" administration defined product derived from infectious agents.

This interest in the role of environment in the etiology of autoimmune diseaseswe had already asked to implement and carry out a campaign of eradication of rheumatic acute in the French Antilles, which helped to eliminate this disease in

less than ten years.

This disease was responsible for the majority of acquired heart disease of children, to the point to represent a leading cause of hospitalization in pediatricwards. Fact Interestingly, in this particular case, the environment does not play a

protective role but a role trigger: the disease is due to the existence of commonantigenic determinants between streptococci and cardiac tissue.

We know that After the great discoveries of François Jacob, André Lwoff andJacques Monod (Nobel Prize in Medicine 1965) and their colleagues fifty yearsago, it was thought that the regulation of gene expression had revealed all itssecrets. One realizes now that as in higher organisms, bacteria and other microorganisms have more diverse strategies previously thought to expressthemselves and adapt. They use so cleverly RNAs to regulate very fine their genes survival, replication, etc. to capture food. These regulations are put to usein all situations encountered by bacteria. Pathogenic bacteria, for example,interact during infection with commensal flora, whether in the gut, skin or other organs (nose, throat, ears ...).

Studies of these complex flora, these "assemblies of microorganisms" grow at a pace incredible. The tools are there: approaches genomic, transcriptomic,

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proteomic, metabolomic can finally have access to understanding the signalsthat regulate the community life of these floras, their composition and balance.And we begin to understand the languages used by chemical bacteria torecognize, to communicate with each other and sometimes work together or

otherwise destroy.

But in our PhD in philosophy of science we have asked the phylosophy of Microbiology

On the philosophy of “the New Microbiology”

and biological Sciences -I

« No doubt the Molecular biology has revolutionized the science of World

kids living in proportions that quantum theory has revolutionized the nuclear physics that there are forty years.

The intense study of the biological functions of living beings. from theanalysis of the structure and molecular interactions gave biochemistryleadership, leading to a relatively new science - molecular biology. In kid time,the establishment of the principle of catalytic functioning of living matter was afundamental for the development of biological science.

The ferments are in many ways incomparably superior to artificial

catalysts. Before their power by any action, thousands of chemical reactions take place in living organisms. Using ferments, in the absence of high temperaturesand pressures, millions and billions of times faster in the presence of the bestchemical catalysts.

The ferments have yet another benefit - the most important. They differ catalysts artificial rationality surprising for their actions, strictly oriented andmaximum efficiency. Each closing act in an optimum manner, without findingtechnological solutions optimal 'in transforming not only one compound or a

group of very close. and transforming them in a direction strictly determined.)

The discovery and description of a growing number of biochemicalreactions â put the agenda the task of trying to establish the fundamental

principles that govern the nature and interdependence of these reactions.Without that. it was impossible to develop a systematic process alive, countless

biochemical terms.

The solution of these problems was first linked two basic discoveriesmade in the thirties and forties and have been essential elements of therevolution in the biological sciences, particularly on the biochemical level. The

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first is the discovery of "conservation." Energy of biochemical reactions in theform of chemical bonds in a particular matter which received the name of adenosine triphosphate. The second is the discovery of the principle of combination reactions in biological systems, ie that the surplus energy formed in

response to a course can be transmitted to another reaction that would not be d'Itself possible.

These two basic discoveries immediately bring the logic in research on the biochemical organization of the activity of cells to distinguish combinationsreactions energy. eligible and ineligible. Thus began the assembly of

biochemical elements in separate groups or mechanisms intact, and when theresearchers took fiai to operate on a certain segment, they found they managedto swallow train, from components, or as Such physiological process whose

biochemists had initiated the development thirty years ago. ' " [7] Thesubsequent progress of science, a deeper penetration of the secrets of lifediscovered was able to process more complex than photosynthesis andrespiration, biochemistry did not yet understand. It was primarily the process of growth and development as well as the phenomena of heredity and itstransmission.

Neither the methods and experiences of physiology, nor those of biochemistry were unable to highlight the properties of living matter whichconstitute the substance of these phenomena. Only with the advent of electron

microscopy that we put into the unknown world of the infinitesimally small particles of the living cell. Thus the practical results of the revolution.Intervened in physics were a powerful catalyst for the revolution in biology. If the power separator ordinary microscope can achieve a magnification of two tothree thousand times, the electron microscope can magnify objects of study of hundreds of thousand times and even more than a million times. The amountconverts to quality basic opportunities have opened to the study of microscopicorganizations, intimate process taking place in the living cell.

In entering ever more deeply into the secrets of the process alive,.Biological science learns about the mechanism for the use of geneticinformation. Thus, biology was brought to explore the giant molecules of organic polymers: nucleic acids, proteins and some carbohydrates, ie training,which play a decisive role in the performance of vital functions essential. Thestudy of these molecules required methods and processes hoc analysis andconstituted one of the key orientations of a science booming molecular biology,we talk a little further.

The results of the biological chemistry were and still are today an grazing

tool knowledge of life processes. But the language of chemistry did not allowitself to penetrate the mysteries of life. The biophysical came to the rescue. The

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search continued for solving the problem of living has enormous methodologicaland practical importance for the development and improvement of material

production,

Academician G. Frank wrote "What we call the living can not betranslated into language purely chemical. In addition to the list of reactionsinvolved in the process of exchanging chemical substances, in addition to thecatalytic reactions and chemical kinetics of these processes, there must be someorganization in space (structure) of all rnacromoléculaires, which is beyond theframework representations purely chemical. "2

This organization, writes G. Frank is not only the location of chemical processes; acting itself is changing, determines their conduct and organise. Thatis why, alongside the chemistry and molecular approaches, we need what might

be called conventional language of 'approaches surmoléculaires "Theseapproachessurmoléculaires can not already under the sole jurisdiction of chemistry and biochemistry. We are witnessing here are qualitatively different

processes and chemicals added to the forces of interaction phenomenacharacteristics of the system surmoléculaire complex. The study of these

phenomena is usually biophysics or physical chemical biology "3 The biologicalsciences naturally attach particular importance nature of the activities of livingorganisms and their smallest components in the cell and components of the cellitself. Science has entered into the inframicroscopique structure of the cell,

which allowed him to make the most unexpected discoveries, forcing a radicalrevision of current ideas on the principles biochemical, biophysical and physico-chemical properties of cellular processes.

"How is born. a new science, a new specialty? "asks P. Thuiflier thy hasnot answered both general and satisfactory this question, although variousassumptions have been made. "4

This interpretation seems skeptical, because the development of a newdiscipline and the birth of a new science does not depend on the identity or theintellectual originality of ideas. Rather, it depends on the character of the natureof the subject of science itself method of exposure in the wider it is the means toachieve an objective, an activity according to a certain orderly fashion. It is bymethodological role that tears the veil to the extraordinary complex phenomenaof nature, society and the human conscience and directs the science to therelease of natural links, objectives, forcing the researcher to stay on Field factsrigorously established. For example, lob jet of molecular biology is to study theevents essential activity vital to their elementary levels in the cell and its

2 G.Frank,L’opinion du savant, Moscou,Editions de l’Académie des Sciences 1963 p.4803 François Jacob Biologie Moléculaire In Atomr 1969 La Recherche p.554 F.Jacob Opus Cit.p.58

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components, the nucleus and the cytoplasm, in the tiny intra-cellular structures,systems the simplest located on the border of living and not living like virus and

bacteriophages, and finally, in systems of biological macromolecular polymersand proteins nuclides acids that carry out its essential functions in training live ...

There is a particularly intensive development of molecular biologyresearch related to problems of proliferation, heredity, structure and. propertiesof macromolecular compounds, their biosynthesis and laws of their reproductionin the process of growth, division and cell development. In other words, biosmacromolecular polymers and nucleic acids are essential objects of research inmolecular biology. Over the past thirty years, biology has undergone a profoundtransformation by the convergence of disciplines for a long time remainedindependent of both the problems they saw as the equipment and methodologythey used. Thus, the cellular physiology, genetics, biochemistry, virology,microbiology have melted into a common discipline, which is now known asthemolecular biology. It aims to interpret the phenomena that take placewithinliving organisms in office structures and functional interrelationships thatoccur between macromolecular constituents of the cell5.

In its first stage, molecular biology has sought to analyze the material thesimplest cell, namely the bacterial cell, that some discoveries were madeaccessible. such a study. In recent years, the elucidation of the main structure of

biological macromolecules, proteins and nucleic acids, the interpretation of their

functions in terms of structure, recognition of their biosynthetic pathways andtheir regulations have renewed our knowledge of heredity and cellular mechanisms. "

This feels the development and differentiation, more interconnection of science that results, models and methods of some sciences are becoming morewidely used in other (for example the use of physical and chemical dodèles in

biology and medicine), and this shows the problem of interdisciplinary research.Another important feature of the current stage of development of science is to

increase the role of constructive elements in scientific knowledge. "On the onehand. In entire body, others share in somatic cell cultures taken from the bodiescomplex.[12] "Because the discovery of the nature and structure of nuclei acidsdemonstrates the rationality of the exceptional nature and organization of hiscreatures, in fact, nucleic acids are composed wholly of four elements: the four nucleotide that does differ from one another by their nitrogen content - adenine,guanine, cytosine, themine. Thus, the tremendous diversity of. life on. Terre A.always a basic biochemical perfectly unique and universal. Moreover, the

principle of complementarity, which explains the old secret of heredity, is one of the essential bases. molecular biology with which it was established that in a

5 V.Enguelgardt Naouka i Jinz 1975 N °5 p II

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DNA molecule, the amount of guanine is always equal to. the amount of cytosine, adenine quantity is a égaie. the amount of themine. During the vitalactivity of the body, the DNA molecules involved in trade undergo manycellular damage under the influence of internal and external factors. Thus, the

new directions of development of molecular biology and its revolutionarycontinuous progress based on solid methodology. "It is the combination of organic synthesis and very fruitful, two methodological approaches. the study of nature and properties of the simplest components of a complex, and the study of the structure, organization, the properties of complex body as a whole, forcesand processes that constitute the system as. Than anything else. The keyquestion is how simple it gives birth to the complex, what are the forces andlaws that are operating here, how to structure new properties of the complexsystem.

It is a focus of scientific research that part of the molecular levels the most primitive and the most basic driving è, levels of organization of increasingcomplexity,. systems with new properties and functions.[ " The essential featureof this passage from simple to complex is an integrated process, we propose theterm of fundamentalism to define the orientation of cognitive science. If oneanalyses the development of natural sciences, technical and social, one findsmuch in common in their methodology and practice.

Thus, this methodology is it absolutely necessary as regards the creation

of automated systems that the development of the vast majority of complex programs, as it is to solve the problems of the relationship between the party andeverything between simple and compound. The need for such a methodologicalapproach is more apparent than ever today as regards the solving of economicand socio-economic and development programmes in which we have alwaysdealing with large complex systems to several components . D'oc current

problem 1 "fundamentalism" for all the natural sciences, technical and social.The mechanism of development of science in their process of unification of thedifferent branches of science plays an important role in guiding scientific

thought and technology of our century. 11 opens two possibilities for developingand refining the material productive forces, through which we can see thedevelopment of the revolution in the natural sciences, technical, socialinteraction and their dialectic in two aspects:

First, humanity will affect so focused on the processes of organic life andfrom it. Raising a colossal effectiveness of social production, and also increasethe possibilities of the man himself - the first productive force of society - andthe perfect considerably.

Secondly, the company will continuously introduce into production theresults of technological and organizational organic life> and. From then allow a

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new scientific and technological revolution which, it has every reason to think,leave it far behind the possibilities opened up by the current scientific andtechnological revolution.

This revolution in the biological sciences wakes up the "technical",“technology "and the organization of operating systems which exceed incomplexity all the systems that man has been able to create and productivityhave never seen in practice the global industry at the same time that capacity, aninfinite number of dimensions, economic performance and reliabilityunimaginable. The active phase of the revolution in the biological sciences

began, it seems, most recently as physics and chemistry, and its practical resultsmay not be as clear and important that the results achieved by physicists andchemists, but it is already visible today that the possibilities, both cognitive and

practical, opened by the revolution in science are of a magnitude that they canserve as a springboard â. a new revolution in science and informationtechnology, which means the development of physical sciences, chemical,

biological as the basis for development and differentiation branches scientificcomputing.6

The question is what relationship established between the development of the New Microbiology and prospects for the future of biological sciences andthe role of philosophy of science from New Microbiology and place of our analysis there are twenty five years philosophical philosophical after the

philosophy of science with the purpose of the symposium Inter Academy?

Position of the philosophical and scientific questions

First, what is microbiology? what is its specialty and originality as scientific and philosophical questions asked? how it relates to the philosophy of science?Secondly what is the philosophy of biology and microbiology new? From the

perspective of the philosophy of dialectical materialist philosophy of science is

based surquoi trends of positivist philosophy and neo positivist? What is his philosophy is based on the creation of the world and the universe? What is thecontribution of participants in the Symposium prospects? What are spotsacademic and scientific problem solving of new microbiology?

Microbiology (from Greek μ ῑ κρος, mīkros, "small"; βίος, bios, "life"; and-λογία, -logia) is the study of microscopic organisms, which are defined as anyliving organism that is either a single cell (unicellular), a cell cluster, or has no

6 Dr Ali KILIC La classification des Sciences et l’Informatique Fondements philosophiques de l’Informatique T pp.hese pour le Doctorat en Philosophie Facculté de Philosophie de l’Universite de Bourgogne 1988 pp.324-330.

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http://en.wikipedia.org/wiki/Ancient_Greek

http://en.wikipedia.org/wiki/Ancient_Greek



cells at all (acellular )7. This includes eukaryotes, such as fungi and protists, and prokaryotes. Viruses[ 8 and prions, though not strictly classed as livingorganisms, are also studied. Microbiology typically includes the study of theimmune system, or Immunology. Generally, immune systems interact with

pathogenic microbes; these two disciplines often intersect which is why manycolleges offer a paired degree such as "Microbiology and Immunology".

Microbiology is a broad term which includes virology, mycology, parasitology, bacteriology, immunology and other branches. A microbiologistis a specialist in microbiology and these related topics.

Microbiological procedures usually must be aseptic, and use a variety of tools such as light microscopes with a combination of stains and dyes.The mostcommonly used stains are called basic dyes, and are composed of positively

charged molecules. Two types of basic dyes are simple stains and differentialstains. simple stains consist of one dye and identify the shape and multicellarrangement of bacteria. Methylene blue, carbolfuchsin, safranin, and crystalviolet are some of the most commonly used stains. Differential stains on theother hand, use two or more dyes and help us to distinguish between two or more organisms or two or different parts of the organism. Types of differentialstains are gram, Ziehl-Neelsen acid fast, negative, flagella, and endospore.Specific constraints apply to particular fields of microbiology, such as

parasitology, which heavily utilizes the light microscopy, whereas microscopy's

utility in bacteriology is limited due to the similarity is many cells physiology.Indeed, most means of differentiating bacteria is based on growth or

biochemical reactions. Virology has very little need for light microscopes,relying on almost entirely molecular means. Mycology relies on all technologiesthe most evenly, from macroscopy to molecular techniques.

Microbiology is actively researched, and the field is advancingcontinuously. It is estimated that only about one percent of the microorganisms

present in a given environmental sample are culturable9 and the number of

bacterial cells and species on Earth is still not possible to be determined, recentestimates indicate that it can be extremely high (5 Exp 30 cells on Earth,unknown number of species). Although microbes were directly observed over three hundred years ago, the precise determination, quantitation and descriptionof its functions is far to be complete, given the overwhelming diversity detected

by genetic and culture-independent means.

7 ^ a b c d e f Madigan M, Martinko J (editors) (2006). Brock Biology of Microorganisms (13th ed.). PearsonEducation. p. 1096. ISBN 0-321-73551-X.8 Rice G (2007-03-27). "Are Viruses Alive?". http://serc.carleton.edu/microbelife/yellowstone/viruslive.html.

Retrieved 2007-07-23.9 Nitesh RAI, Ludwig W, Schleifer KH (2011). "Phylogenetic identification and in situ detection of individualmicrobial cells without cultivation". Microbiology Rev. 59 (1):

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http://en.wikipedia.org/wiki/International_Standard_Book_Number

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http://serc.carleton.edu/microbelife/yellowstone/viruslive.html

http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=239358









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http://en.wikipedia.org/wiki/Eukaryote

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http://en.wikipedia.org/wiki/Pathogen

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The existence of microorganisms was hypothesized for many centuries before their actual discovery. The existence of unseen microbiological life was postulated by Jainism which is based on Mahavira’s teachings as early as 6thcentury BCE.10 Paul Dundas notes that Mahavira asserted existence of unseen

microbiological creatures living in earth, water, air and fire.11

Jain scriptures alsodescribe nigodas which are sub-microscopic creatures living in large clustersand having a very short life and are said to pervade each and every part of theuniverse, even in tissues of plants and flesh of animals.12 The Roman MarcusTerentius Varro made references to microbes when he warned against locating ahomestead in the vicinity of swamps "because there are bred certain minutecreatures which cannot be seen by the eyes, which float in the air and enter the

body through the mouth and nose and there by cause serious diseases.13"

In 1546 Girolamo Fracastoro proposed that epidemic diseases werecaused by transferable seedlike entities that could transmit infection by direct or indirect contact, or vehicle transmission.14[

However, early claims about the existence of microorganisms werespeculative, and not based on microscopic observation. Actual observation anddiscovery of microbes had to await the invention of the microscope in the 17thcentury.

Anton van Leeuwenhoek , is considered to be the first to observe

microorganisms using a microscope.In 1676, Anton van Leeuwenhoek observed bacteria and other microorganisms, using a single-lens microscope of his own design While Van Leeuwenhoek is often cited as the first to observemicrobes, Robert Hooke made the first recorded microscopic observation, of thefruiting bodies of molds, in 1665 The first observation of microbes using amicroscope is generally credited to the Dutch draper and haberdasher, Antonievan Leeuwenhoek, who lived for most of his life in Delft, Holland. It has,however, been suggested that a Jesuit priest called Athanasius Kircher was thefirst to observe micro-organisms.[10] He was among the first to design magic

lanterns for projection purposes, so he must have been well acquainted with the properties of lenses.[10] One of his books contains a chapter in Latin, which readsin translation – ‘Concerning the wonderful structure of things in nature,investigated by Microscope. Here, he wrote ‘who would believe that vinegar andmilk abound with an innumerable multitude of worms.’ He also noted that putrid

10 Mahavira is dated 599 BCE - 527 BC. See. Dundas, Paul; John Hinnels ed. (2002). The Jain. London:Routledge. ISBN 0-415-26606-8. p. 2411 Dundas, Paul (2002) p. 8812 aini, Padmanabh (1998). The Jaina Path of Purification. New Delhi: Motilal Banarsidass. ISBN 81-208-1578-5. p. 109

13 Varro on Agriculture 1, xii Loeb.14 Fracastoro, Girolamo (1546), De Contagione et Contagiosis Morbis transl. Wilmer Cave Wright (1930). NewYork: G.P. Putnam's

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material is full of innumerable creeping animalcule. These observations antedateRobert Hooke’s Micrographia by nearly 20 years and were published some 29years before van Leeuwenhoek saw protozoa and 37 years before he describedhaving seen bacteria.

Innovative laboratory glassware and experimental methods developed by Louis Pasteur and other biologists contributed to the young field of bacteriology in the late 19th century.

The field of bacteriology (later a subdiscipline of microbiology) wasfounded in the 19th century by Ferdinand Cohn, a botanist whose studies onalgae and photosynthetic bacteria led him to describe several bacteria including

Bacillus and Beggiatoa. Cohn was also the first to formulate a scheme for thetaxonomic classification of bacteria and discover spores. Louis Pasteur andRobert Koch were contemporaries of Cohn’s and are often considered to be thefather of microbiology and medical microbiology, respectively. Pasteur is mostfamous for his series of experiments designed to disprove the then widely heldtheory of spontaneous generation, thereby solidifying microbiology’s identity asa biological science.Pasteur also designed methods for food preservation( pasteurization) and vaccines against several diseases such as anthrax, fowlcholera and rabies. Koch is best known for his contributions to the germ theor of

disease, proving that specific diseases were caused by specific pathogenicmicro-organisms. He developed a series of criteria that have become known asthe Koch's postulates. Koch was one of the first scientists to focus on theisolation of bacteria in pure culture resulting in his description of several novel

bacteria including Mycobacterium tuberculosis, the causative agent of tuberculosis.

While Pasteur and Koch are often considered the founders of microbiology, their work did not accurately reflect the true diversity of themicrobial world because of their exclusive focus on micro-organisms havingdirect medical relevance. It was not until the late 19th century and the work of

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Martinus Beijerinck and Sergei Winogradsky, the founders of general

microbiology (an older term encompassing aspects of microbial physiology,diversity and ecology), that the true breadth of microbiology was revealed.[1]

Beijerinck made two major contributions to microbiology: the discovery of

viruses and the development of enrichment culture techniques.[

While his work on the Tobacco Mosaic Virus established the basic principles of virology, it washis development of enrichment culturing that had the most immediate impact onmicrobiology by allowing for the cultivation of a wide range of microbes withwildly different physiologies. Winogradsky was the first to develop the conceptof chemolithotrophy and to thereby reveal the essential role played by micro-organisms in geochemical processes. He was responsible for the first isolationand description of both nitrifying and nitrogen-fixing bacteria.

The philosophy of biology

The philosophy of biology is a subfield of philosophy of science, whichdeals with epistemological, metaphysical, and ethical issues in the biologicaland biomedical sciences. Although philosophers of science and philosophersgenerally have long been interested in biology (e.g., Aristotle, Descartes, andeven Kant), philosophy of biology only emerged as an independent field of

philosophy in the 1960s and 1970s. Philosophers of science then began payingincreasing attention to biology, from the rise of Neodarwinism in the 1930s and1940s to the discovery of the structure of DNA in 1953 to more recent advances

in genetic engineering. Other key ideas include the reduction of all life processesto biochemical reactions, and the incorporation of psychology into a broader neuroscience.

The philosophy of biology can be seen as following an empirical tradition,favoring naturalism . Many contemporary philosophers of biology have largelyavoided traditional questions about the distinction between life and non-life.Instead, they have examined the practices, theories, and concepts of biologistswith a view toward better understanding biology as a scientific discipline (or

group of scientific fields). Scientific ideas are philosophically analyzed and their consequences are explored. It is sometimes difficult to delineate philosophy of

biology as separate from theoretical biology. A few of the questions philosophers of biology have attempted to answer, for example, include:

"What is a biological species?" "How is rationality possible, given our biological origins?" "How do organisms coordinate their common behavior?""Are there genome editing agents?" "How might our biological understandingsof race, sexuality, and gender reflect social values?" "What is natural selection,and how does it operate in nature?" "How do medical doctors explain disease?"

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"From where do language and logic stem?"; "How is ecology related tomedicine?"

A subset of philosophers of biology with a more explicitly naturalistic

orientation hope that biology will provide scientific answers to suchfundamental problems of epistemology, ethics, aesthetics, anthropology andeven metaphysics. Furthermore, progress in biology urges modern societies torethink traditional values concerning all aspects of human life. The possibility of genetic modification of human stem cells, for example, has led to an ongoingcontroversy on how certain biological techniques could infringe upon ethicalconsensus (see bioethics). Some of the questions addressed by these

philosophers of biology include: "What is life?" "What makes humans uniquelyhuman?"; "What is the basis of moral thinking?";"What are the factors we usefor aesthetic judgments?"; "Is evolution compatible with Christianity or other religious systems?"

Increasingly, ideas drawn from philosophical ontology and logic are beingused by biologists in the domain of bioinformatics. Ontologies such as the GeneOntology are being used to annotate the results of biological experiments in avariety of model organisms in order to create logically tractable bodies of dataavailable for reasoning and search. The Gene Ontology itself is a species-neutralgraph-theoretical representation of biological types joined together by formallydefined relations.

Marjorie Grene, David Depew15 have combined forces to produce anepisodic history of the philosophy of biology from Aristotle to the present.As the title of this book implies, they are writing a history of the

philosophy of biology, not a history of biology. Even so, in writing ahistory of the philosophy of biology, they cannot very well ignore biology.Grene and Depew begin dealing with life itself. Evolution, as it should,comes in only much later.

The first four chapters of their book concern the views of a half dozen of the most important scholars ranging from Aristotle and the Aristotelians toWilliam Harvey, Descartes and Newton. These chapters range over twothousand year--from the fourth century BC to the 17th century. As might beexpected these discussions are abbreviated but hardly superficial. Grene andDepew have to deal not only with the writings of these men but also the highlytechnical secondary literature that has grown up around them. I am afraid that

15The Philosophy of Biology: An Episodic History Published: January 02, 2005 Grene, Marjorie and David Depew, The

Philosophy of Biology: An Episodic History, Cambridge University Press, 2004, 438pp, $29.99 (pbk), ISBN0521643805. Reviewed by David Hull, Northwestern University

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most readers, excluding professional philosophers, will find the chapters onAristotle and the Aristotelians formidable, but they are worth studying. No oneis better able to explain Aristotle and his "biology" than is Marjorie Grene. Her introductory text on Aristotle remains in print to this day.

One of the purposes of these early chapters is to show that the contrast between physics and biology has been around from the beginning of Westernthought. Grene and Depew note that the "subject matter of biology hassomething about it that is not quite the same as physics" (p. xv). One of thechallenges that Grene and Depew face is that two of the major figures whomthey treat--Descartes and Newton--were far more concerned with physics thanwith biology. Aristotle and Harvey were certainly "biologists." Descartes and

Newton were not.

Kant opposed polygenism and supported his position by reference toBuffon's species concept. The contrast is between species as eternal formsdefined in terms of essential characteristics (perhaps clusters) or as historicalentities maintained by successive breeding (p. 80). Are species kinds ( Arten),lineages (Gattungen) or both (p. 118)? Life would be easier if these two speciesconcepts always divided up the living world in the same way, but they don't.Because miscegenation was far from unknown at the time, Kant concluded thatall human beings belong to a single species. In the following century, a temporaldimension was added to this dispute. One species might split into two or more

species, and a single species might have its origin in two or more species.

As always Darwin provides the watershed for biology. Geology was the chief impetus. In addition, British scientists took it on themselves to develop

philosophy of science as a professional discipline, just in time to be confronted by a theory that seriously challenged their philosophies. John Herschel andWilliam Whewell were the founding fathers of philosophy of science in GreatBritain, and in the case of Whewell at least biology played a role. For somereason, Grene and Depew do not discuss John Stuart Mill at any length, possibly

because he came along later. What is disturbing is that all three of these men--the very men who devoted a good part of their professional lives studyingscience as science--rejected Darwin's theory. Species do not evolve, and if theydo, they certainly do not do so by means of natural selection--the law of higgledy piggledy.

After the chapter on Darwin, Grene and Depew proceed along a familiar path beginning with the "non-rediscovery" of Mendel's laws at the turn of thecentury. In the early years scientists tended to refer to the "discovery" of Mendel's laws, but historians were put off. Mendel discovered these laws. At the

turn of the century, they were "rediscovered." Then later as historians dug moredeeply into the literature, they decided that their predecessors had seriously

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misunderstood Mendel, reading present-day concerns into his work. Mendel wasno Mendelian. Hence, the early "rediscovers" of Mendel's laws were actually"non-rediscoverers."

The contrast between philosophers and scientists is even harder to draw.For example, most people today think of Descartes as a philosopher and Newtonas a scientist because of the very different fates that their work received, but intheir day Descartes and Newton were engaged in much the same array of activities. Present-day philosophy of biology and biology merge seamlessly.Both philosophers and biologists contribute to this endeavor. In this penultimatechapter of their book, Grene and Depew evaluate the contributions made by

biologists and philosophers of biology to such issues as the species problem,reducibility, function and teleology--issues that have been debated in some formor other from Aristotle to the present.

In the final chapter, Grene and Depew address a grab bag of topics thatare not all that related to the book as a whole--the descent of man, polygenismand monogenism once again, the nature/nurture controversy, brains, language,mind and the human genome project. Because of my own interests, I might beexcused for treating one issue in my own work that Grene and Depew discuss--the metaphysical status of species as the things that evolve. A fairly standarddistinction in philosophy from at least Plato and Aristotle to the present is

between classes and individuals. The terms change, but the distinction remains

fairly constant. Classes are groups or sets of entities. All the planets in theuniverse form a class. A subset of these classes is important because theyfunction in laws of nature -- at least for those philosophers who think that suchthings as laws of nature exist. Even though the universe is finite, laws of natureare commonly characterized as being spatiotemporally unrestricted. Hence, theclasses that function in them must also be spatiotemporally unrestricted.

Some philosophers of biology have attempted to explain the rise and fallof reductionism, vitalism, and holism throughout the history of biology. For

example, these philosophers claim that the ideas of Charles Darwin ended thelast remainders of teleological views from biology. Debates in these areas of philosophy of biology turn on how one views reductionism.

An autonomous philosophy of biology

All processes in organisms obey physical laws, the difference frominanimate processes lying in their organisation and their being subject to control

by coded information. This has led some biologists and philosophers (for example, Ernst Mayr and David Hull) to return to the strictly philosophical

reflections of Charles Darwin to resolve some of the problems which confrontedthem when they tried to employ a philosophy of science derived from classical

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physics. This latter, positivist approach emphasised a strict determinism (asopposed to high probability) and to the discovery of universally applicable laws,testable in the course of experiment. It was difficult for biology, beyond a basicmicrobiological level, to live up to these structures. Standard philosophy of

science seemed to leave out a lot of what characterised living organisms -namely, a historical component in the form of an inherited genotype.

Biologists with philosophic interests responded, emphasising the dualnature of the living organism. On the one hand there was the genetic programme(represented in nucleic acids) - the genotype. On the other there was its extended

body or soma - the phenotype. In accommodating the more probabilistic andnon-universal nature of biological generalisations, it was a help that standard

philosophy of science was in the process of accommodating similar aspects of 20th century physics.

This led to a distinction between proximate causes and explanations -"how" questions dealing with the phenotype; and ultimate causes - "why"questions, including evolutionary causes, focused on the genotype. Thisclarification was part of the great reconciliation, by Ernst Mayr, among others,in the 1940s, between Darwinian evolution by natural selection and the geneticmodel of inheritance. A commitment to conceptual clarification hascharacterised many of these philosophers since. Trivially, this has reminded usof the scientific basis of all biology, while noting its diversity - from

microbiology to ecology. A complete philosophy of biology would need toaccommodate all these activities. Less trivially, it has unpacked the notion of "teleology". Since 1859, scientists have had no need for a notion of cosmicteleology - a programme or a law that can explain and predict evolution. Darwin

provided that. But teleological explanations (relating to purpose or function)have remained stubbornly useful in biology - from the structural configurationof macromolecules to the study of co-operation in social systems. By clarifyingand restricting the use of the term to describe and explain systems controlledstrictly scientifically by genetic programmes, or other physical systems,

teleological questions can be framed and investigated while remainingcommitted to the physical nature of all underlying organic processes.

Similar attention has been given to the concepts of natural selection (whatis the target of natural selection? - the individual? the environment? the genome?the species?); adaptation; diversity and classification; species and speciation;and macroevolution.

Just as biology has developed as an autonomous discipline in fullconversation with the other sciences, there is a great deal of work now being

carried on by biologists and philosophers to develop a dedicated philosophy of biological science which, while in full conversation with all other philosophic

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disciplines, attempts to give answers to the real questions raised by scientificinvestigations in biology.

Other perspectives

While the overwhelming majority of English-speaking scholars operatingunder the banner of " philosophy of biology" work within the Anglo-Americantradition of analytical philosophy, there is a stream of philosophic work incontinental philosophy which seeks to deal with issues deriving from biologicalscience. The communication difficulties involved between these two traditionsare well known, not helped by differences in language. Gerhard Vollmer is oftenthought of as a bridge but, despite his education and residence in Germany, helargely works in the Anglo-American tradition, particularly pragmatism, and isfamous for his development of Lorenz's and Quine's idea of evolutionary

epistemology. On the other hand, one scholar who has attempted to give a morecontinental account of the philosophy of biology is Hans Jonas. His "The

Phenomenon of Life" (New York, 1966) sets out boldly to offer an "existential

interpretation of biological facts", starting with the organism's response tostimulus and ending with man confronting the Universe, and drawing upon adetailed reading of phenomenology. This is unlikely to have much influence onmainstream philosophy of biology, but indicates, as does Vollmer's work, thecurrent powerful influence of biological thought on philosophy. A moreengaging account is given by the late Virginia Tech philosopher Marjorie Grene.

The growth of philosophical interest in biology over the past thirty yearsreflects the increasing prominence of the biological sciences in the same period.There is now an extensive literature on many different biological topics, and itwould be impossible to summarise this body of work in this single entry.Instead, this entry sets out to explain what philosophy of biology is. Why does

biology matter to philosophy and vice versa? A list of the entries in theencyclopedia which address specific topics in the philosophy of biology is

provided at the end of the entry.

Three different kinds of philosophical enquiry fall under the generalheading of philosophy of biology. First, general theses in the philosophy of science are addressed in the context of biology. Second, conceptual puzzleswithin biology itself are subjected to philosophical analysis. Third, appeals to

biology are made in discussions of traditional philosophical questions. The firsttwo kinds of philosophical work are typically conducted in the context of adetailed knowledge of actual biology, the third less so.

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Philosophy of biology can also be subdivided by the particular areas of biological theory with which it is concerned. Biology is a diverse set of disciplines, ranging from historical sciences such as paleontology to engineeringsciences such as biotechnology. Different philosophical issues occur in each

field. The latter part of the entry discusses how philosophers have approachedsome of the main disciplines within biology.

1. Pre-history of Philosophy of Biology 2. Three Types of Philosophy of Biology.3. Philosophy of Evolutionary Biology 4. Philosophy of SystematicBiology 5. Philosophy of Molecular Biology.6. Philosophy of DevelopmentalBiology.7. Philosophy of Ecology and Conservation Biology.8. Methodology inPhilosophy of Biology

1. Pre-history of Philosophy of Biology

As is the case for most apparent novelties, closer inspection reveals a prehistoryfor the philosophy of biology. In the 1950's the biologist J. H Woodger and the

philosopher Morton Beckner both published major works on the philosophicalof biology (Woodger 1952; Beckner 1959), but these did not give rise to asubsequent philosophical literature. Some philosophers of science also madeclaims about biology based on general epistemological and metaphysicalconsiderations. Perhaps the most famous example is J. J. C Smart's claim thatthe biology is not an autonomous science, but a technological application of

more basic sciences, like ‘radio-engineering’ (Smart 1959, 366). Likeengineering, biology cannot make any addition to the laws of nature. It can onlyreveal how the laws of physics and chemistry play out in the context of

particular sorts of initial and boundary conditions. Even in 1969 the zoologistErnst Mayr could complain that books with ‘philosophy of science’ in the titlewere all misleading and should be re-titled ‘philosophy of physics’ (Mayr 1969).The encouragement of prominent biologists such as Mayr and F.J Ayala (Ayala1976; Mayr 1982) was one factor in the emergence of the new field. The firstsign of philosophy of biology becoming a mainstream part of philosophy of

science was the publication of David Hull's Philosophy of Biological Science inthe prominent Prentice-Hall Foundations of Philosophy series (Hull 1974). Fromthen on the field developed rapidly. Robert Brandon could say of the late 1970'sthat “I knew five philosophers of biology: Marjorie Grene, David Hull, MichaelRuse, Mary Williams and William Wimsatt.” (Brandon 1996, xii–xiii) By 1986,however, there were more than enough to fill the pages of Michael Ruse's new

journal Biology and Philosophy.

2. Three Types of Philosophy of Biology

Three different kinds of philosophical enquiry fall under the generalheading of philosophy of biology. First, general theses in the philosophy of

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science are addressed in the context of biology. Second, conceptual puzzleswithin biology itself are subjected to philosophical analysis. Third, appeals to

biology are made in discussions of traditional philosophical questions. The firstmajor debate in the philosophy of biology exemplified the first of these, the use

of biological science to explore a general theme in philosophy of science.Kenneth F. Schaffner applied the logical empiricist model of theory reduction tothe relationship between classical, Mendelian genetics and the new molecular genetics (Schaffner 1967a; Schaffner 1967b; Schaffner 1969). David Hullargued that the lesson of this attempt was that Mendelian genetics is irreducibleto molecular genetics (Hull 1974; Hull 1975). This debate reinforced the near-consensus in the 1970's and 1980's that the special sciences are autonomousfrom the more fundamental sciences (Fodor 1974; Kitcher 1984). However, theapparent absurdity of the claim that the molecular revolution in biology was nota successful instance of scientific reduction also led the formulation of increasingly more adequate models of theory reduction (Wimsatt 1976; Wimsatt1980; Schaffner 1993; Waters 1994; Sarkar 1998).

In another important early debate philosophers set out to solve aconceptual puzzle within biology itself. The concept of reproductive fitness is atthe heart of evolutionary theory, but its status has always been problematic. Ithas proved surprisingly hard for biologists to avoid the criticism that, “[i]f wetry to make laws of evolution in the strict sense we seem to reduce totautologies. Thus suppose we say that even in Andromeda ‘the fittest will

survive’ we say nothing, for ‘fittest’ has to be defined in terms of ‘survival’”(Smart 1959, 366). In the 1970's the new generation of philosophers of biology

began by noting that fitness is a supervenient property of organisms: the fitnessof each particular organism is a consequence of some specific set of physicalcharacteristics of the organism and its particular environment, but twoorganisms that have identical levels of fitness may do so in virtue very differentsets of physical characteristics (Rosenberg 1978). Alexander Rosenberg andMary B. Williams went on to argue that fitness is an irreducible primitive whichderives its meaning from its place in an axiomatic formulation of evolutionary

theory (Rosenberg 1983; Sober 1984a; Williams and Rosenberg 1985). But byfar the most widely-favoured solution to the ‘tautology problem’ was to arguethat this supervenient property is a propensity—a probability distribution over

possible numbers of offspring (Mills and Beatty 1979). Although fitness isdefined in terms of reproductive success, it is not a tautology that the fittestorganisms have the most offspring, any more than it is a tautology that dice

produce even numbers more often than they produce sixes. The propensities of fit organisms to survive and of dice to fall equally often on each side both allowus to make fallible predictions about what will happen, predictions that become

more reliable as the size of the sample increases. It remains unclear, however,

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whether it is possible to specify a probability distribution or set of distributionsthat can play all the roles actually played by fitness in population biology.

The phrase ‘conceptual puzzles’ should be understood very broadly. The

conceptual work done by philosophers of biology in many cases mergessmoothly into theoretical biology. It also sometimes leads philosophers tocriticise the chains of argument constructed by biologists, and thus to enter directly into ongoing biological debates. In the same way, the first kind of

philosophy of biology I have described—the use of biological examples to work through general issues in the philosophy of science—sometimes feeds back into

biology itself through specific recommendations for improving biologicalmethodology. It is a striking feature of the philosophy of biology literature that

philosophers often publish in biology journals and that biologists oftencontribute to philosophy of biology journals. The philosophy of biology also hasa potentially important role as a mediator between biology and society. Popular representations of biology derive broad lessons from large swathes of experimental findings. Philosophers of science have an obvious role inevaluating these interpretations of the significance of specific biological findings(Stotz and Griffiths 2008).

A third form of philosophy of biology occurs when philosophers appeal to biology to support positions on traditional philosophical topics, such as ethics or epistemology. The extensive literature on biological teleology is a case in point.

After a brief flurry of interest in the wake of the ‘modern synthesis’, duringwhich the term ‘teleonomy’ was introduced to denote the specificallyevolutionary interpretation of teleological language (Pittendrigh 1958), the ideasof function and goal directedness came to be regarded as relativelyunproblematic by evolutionary biologists. In the 1970's, however, philosophersstarted to look to biology to provide a solid, scientific basis for normativeconcepts, such as illness or malfunction (Wimsatt 1972; Wright 1973; Boorse1976). Eventually, the philosophical debate produced an analysis of teleologicallanguage fundamentally similar to the view associated with modern synthesis

biology (Millikan 1984; Neander 1991). According to the ‘etiological theory’ of function, the functions of a trait are those activities in virtue of which the traitwas selected. The idea of ‘etiological’ or ‘proper’ function has become part of the conceptual toolkit of philosophy in general and of the philosophy of language and the philosophy of mind in particular.

3. Philosophy of Evolutionary Biology

Philosophy of biology can also be subdivided by the particular areas of biological theory with which it is concerned. Until recently, evolutionary theory

has attracted the lion's share of philosophical attention. This work hassometimes been designed to support a general thesis in the philosophy of

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science, such as the ‘semantic view’ of theories (Lloyd 1988). But most of thiswork is concerned with conceptual puzzles that arise inside the theory itself, andthe work often resembles theoretical biology as much as pure philosophy of science. Elliott Sober's classic study The Nature of Selection: Evolutionary

theory in philosophical focus (Sober 1984b) marks the point at which most philosophers became aware of the philosophy of biology. Sober analyzed thestructure of explanations in population genetics via an analogy with thecomposition of forces in dynamics, treating the actual change in genefrequencies over time as the result of several different ‘forces’, such as selection,drift, and mutation. This sort of careful, methodological analysis of populationgenetics, the mathematical core of conventional evolutionary theory, continuesto give rise to interesting results (Pigliucci and Kaplan 2006; Okasha 2007).

The intense philosophical interest in evolutionary theory in the 1980's can partly be explained by the controversies over ‘sociobiology’ that were provoked by the publications of E.O. Wilson's eponymous textbook (Wilson 1975) andstill more by Richard Dawkins's The Selfish Gene (Dawkins 1976). The claimthat the real unit of evolution is the individual Mendelian allele created anexplosion of philosophical work on the ‘units of selection’ question (Brandonand Burian 1984) and the issue of ‘adaptationism’ (Dupré 1987). Arguably,

philosophers made a significant contribution to the rehabilitation of some formsof ‘group selection’ within evolutionary biology in the 1990's, following twodecades of neglect (Sober and Wilson 1998).

The debates over ‘adaptationism’ turned out to involve a diffuse set of worries about whether evolution produces optimal designs, the methodologicalrole of optimality assumptions, and the explanatory goals of evolutionary theory.Philosophical work has helped to distinguish these strands in the debate andreduce the confusion seen in the heated and polemical biological literature for and against ‘adaptationism’ (Orzack and Sober 2001).

4. Philosophy of Systematic Biology

Philosophical discussion of systematics was a response to a ‘scientificrevolution’ in that discipline in the 1960's and 1970's, a revolution which sawthe discipline transformed first by the application of quantitative methods, andthen by the ‘cladistic’ approach, which argues that the sole aim of systematicsshould be to represent the evolutionary relationships between groups of organisms (phylogeny). Ideas from the philosophy of science were used to arguefor both transformations, and the philosopher David L. Hull was an active

participant in scientific debates throughout these two revolutions (Hull 1965;Hull 1970; Hull 1988; see also Sober 1988).

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The biologist Michael Ghiselin piqued the interest of philosophers whenhe suggested that systematics was fundamentally mistaken about the ontologicalstatus of biological species (Ghiselin 1974). Species are not types of organismsin the way that chemical elements are types of matter. Instead, they are historical

particulars like nations or galaxies. Individual organisms are not instances of species, as my wedding ring is an instance of gold. Instead, they are parts of species, as I am a part of my family. As Smart had earlier noticed, this has theimplication that there can be no ‘laws of nature’ about biological species, at leastin the traditional sense of laws true at every time and place in the universe(Smart 1959). This has led some philosophers of biology to argue for a newconception of laws of nature (Mitchell 2000).

However, the view that species are ‘individuals’ leaves other importantquestions about species unsolved and raises new problems of its own. Aroundtwenty different so-called ‘species concepts’ are represented in the current

biological literature, and the merits, interrelations, and mutual consistency or inconsistency of these has been a major topic of philosophical discussion.

Biological species are one of the classic examples of a ‘natural kind’. The philosophy of systematics has had a major influence on recent work onclassification and natural kinds in the general philosophy of science (Dupré1993; Wilson 1999).

5. Philosophy of Molecular Biology

I mentioned above that the reduction of Mendelian genetics to molecular genetics one of the first topics to be discussed in the philosophy of biology. Theinitial debate between Schaffner and Hull was followed by the so-called ‘anti-reductionist consensus’ (Kitcher 1984). The reductionist position was revived ina series of important papers by Kenneth Waters (Waters 1990; Waters 1994) anddebate over the cognitive relationship between the two disciplines continuestoday, although the question is not now framed as a simple choice betweenreduction and irreducibility. Lindley Darden, Schaffner and others have arguedthat explanations in molecular biology are not neatly confined to one ontologicallevel, and hence that ideas of ‘reduction’ derived from classical examples likethe reduction of the phenomenological gas laws to molecular kinematics innineteenth century physics are simply inapplicable (Darden and Maull 1977;Schaffner 1993). Moreover, molecular biology does not have the kind of grandtheory based around a set of laws or a set of mathematical models that isfamiliar from the physical sciences. Instead, highly specific mechanisms thathave been uncovered in detail in one model organism seem to act as ‘exemplars’allowing the investigation of similar, although not necessarily identical,

mechanisms in other organisms that employ the same, or related, molecular interactants. Darden and others have argued that these ‘mechanisms’—specific

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collections of entities and their distinctive activities—are the fundamental unitof scientific discovery and scientific explanation, not only in molecular biology,

but in a wide range of special sciences (Machamer, Darden et al. 2000; see alsoBechtel and Richardson 1993).

Another important topic in the philosophy of molecular biology has beenthe definition of the gene (Beurton, Falk and Rheinberger 2000; Griffiths andStotz 2007). Philosophers have also written extensively on the concept of genetic information, the general tenor of the literature being that it is difficult toreconstruct this idea precisely in a way that does justice to the apparent weight

placed on it by molecular biologists (Sarkar 1996; Maynard Smith 2000;Griffiths 2001; Jablonka 2002).

6. Philosophy of Developmental Biology

The debates over ‘adaptationism’ in the 1980's made philosophersfamiliar with the complex interactions between explanations of traits inevolutionary biology and explanations of the same traits in developmental

biology. Developmental biology throws light on the kinds of variation that arelikely to be available for selection, posing the question of how far the results of evolution can be understood in terms of the options that were available(‘developmental constraints’) rather than the natural selection of those options(Maynard Smith, Burian et al. 1985). The debate over developmental constraints

looked at developmental biology solely from the perspective of whether it could provide answers to evolutionary questions. However, as Ron Amundson pointedout, developmental biologists are addressing questions of their own, and, heargued, a different concept of ‘constraint’ is needed to address those questions(Amundson 1994). The emergence in the 1990's of a new field promising tounite both kinds of explanation, evolutionary developmental biology, has givenrise to a substantial philosophical literature aimed at characterizing this fieldfrom a methodological viewpoint (Maienschein and Laublicher 2004; Robert2004; Amundson 2005; Brandon and Sansom 2007).

7. Philosophy of Ecology and Conservation Biology

Until recently this was a severely underdeveloped field in the philosophyof biology. This is surprising, because there is obvious potential for all three of the approaches to philosophy of biology discussed above. There is also asubstantial body of philosophical work in environmental ethics, and it seemsreasonable to suppose that answering the questions that arise there would requirea critical examination of ecology and conservation biology. In fact, an important

book which sought to provide just those underpinnings—Kristin Shrader-

Frechette and Earl McCoy's Method in Ecology: Strategies for Conservation

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(1993)—was an honorable exception to the philosophical neglect of ecology inearlier decades.

In the past decade philosophers have started to remedy the neglect of

ecology and a number of major books have appeared (Cooper 2003, Ginzburgand Colyvan 2004, Sarkar 2005, MacLaurin and Sterelny 2008). Discussion hasfocused on the troubled relationship between mathematical models andempirical data in ecology, on the idea of ecological stability and the 'balance of nature', and on the definition of biodiversity.

8. Methodology in Philosophy of Biology

Most work in the philosophy of biology is self-consciously naturalistic,recognizing no profound discontinuity in either method or content between

philosophy and science. Ideally, philosophy of biology differs from biologyitself not in its knowledge base, but only in the questions it asks. The

philosopher aims to engage with the content of biology at a professional level,although typically with greater knowledge of its history than biologiststhemselves, and less hands-on skills. It is common for philosophers of biology tohave academic credentials in the fields that are the focus of their research, and to

be closely involved with scientific collaborators. Philosophy of biology'snaturalism and the continuity of its concerns with science itself is shared withmuch other recent work in the philosophy of science, perhaps most notably in

the philosophy of neuroscience (Bechtel, Mandlik et al. 2001).

Even the distinction between the questions of biology and those of philosophy of biology is not absolutely clear. As noted above, philosophers of biology addressthree types of questions: general questions about the nature of science,conceptual puzzles within biology, and traditional philosophical questions thatseem open to illumination from the biosciences. When addressing the secondsort of question, there is no clear distinction between philosophy of biology andtheoretical biology. But while this can lead to the accusation that philosophers of

biology have abandoned their calling for ‘amateur hour biology’ it can equallywell be said that a book like The Selfish Gene (Dawkins 1976) is primarily acontribution to philosophical discussion of biology. Certainly, the professionalskills of the philosopher are as relevant to these internal conceptual puzzles asthey are to the other two types of question. All three types of questions can berelated to the specific findings of the biological sciences only by complex chainsof argument.

INTER-ACADEMY SYMPOSIUM-II

Académie des sciences, German National Academy of Sciences

Leopoldina and The Royal Society on “The New Microbiology”

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In the InterAcademy symposion after the opening made by Jean Bach perpetual secretary of the Academy of Sciences is Prof.Jorg Vogel spoke. The prose of his presentation is An RNA perspective on bad microbes and their

eukaryotic hosts.

According to Jörg Vogel16m Institute for Molecular Infection Biology,University of Würzburg, Germany This talk will discuss emerging concepts andmechanisms of gene regulation by small noncoding RNAs (sRNAs) in bacteria,for example, programmed target mRNA decay, seed pairing, and 3’ adenosinedependence of those sRNAs that act by the common RNA chaperone, Hfq.Furthermore, I will present examples of how RNA deep sequencingtechnologies have been facilitating new approaches to the global discovery andfunctional study of diverse functional sRNAs in many bacterial species, and howthese can be used for parallel analysis of gene expression programs in a bacterial

pathogen and its eukaryotic.

The RNA Biology group is interested in gene regulation by noncodingRNA molecules in bacterial pathogens and eukaryotic host cells. We use a widerange of biochemical, genetic, biocomputational and RNA deep sequencingapproaches to discover new regulatory RNA molecules and their functions. Our work is aided by many fruitful collaborations with laboratories in Germany,Europe and overseas.

Research

Small regulatory RNAs in bacteria

A major focus of our research is in small regulatory RNAs (sRNAs) thatassociate with the conserved RNA-binding protein Hfq in the model pathogenSalmonella Typhimurium. Hfq-dependent sRNAs constitute the largest post-transcriptional network presently known in bacteria, rivaling the complex

16 2009 Full Professor and Chair, Institute for Molecular Infection Biology University of Würzburg, Germany 2004 – 2010

Max Planck Research Group Leader (W2) RNA Biology group, MPI for Infection Biology, Berlin, Germany Ph.D. student

and Postdoc at Humboldt University Berlin, Germany Ph.D. thesis: “Group II intron splicing in higher plant chloroplasts”,supervised by Thomas Börner and Wolfgang Hess, Department of Genetics 1991 – 1996 Undergraduate Studies inBiochemistry Humboldt University, Berlin, Germany Imperial College, London, UK

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regulations by eukaryotic microRNAs. Salmonella expresses ~100 sRNAs from both core genomic regions that are conserved in closely related Escherichia coli

and from Salmonella-specific, pathogenicity islands. The Hfq-dependent sRNAstypically modulate protein synthesis by using short imperfect base-pairing with

target mRNAs, thus altering translation and stability of the mRNA. We nowunderstand that a single sRNA can regulate many target mRNAs using a highly-conserved short (≥7 nucleotide) seed sequence, yet how sRNAs act select withhigh specificity their targets in the background of thousands of other cellular transcripts is not understood. Equally, do proteins other than Hfq help mediatesRNA activity? Other fundamental questions which we are addressing are whatare the benefits of using an RNA regulator versus a transcriptional factor incomplex regulatory networks; how are the sRNAs themselves regulated; andhow does this relate to virulence.

RNA sequencing

Massively parallel sequencing of cellular transcripts has beenrevolutionizing the discovery of coding and noncoding RNAs in virtually anyorganism. We were one of the first groups to use RNA deep sequencing in

bacteria, and developed generic methods such as differential RNA sequencing(dRNA-seq) to report the primary transcriptomes of the major human pathogen,

Helicobacter pylori, and many other species. We also pioneered the use of deepsequencing to identify the interaction partners of bacterial RNA binding

proteins, for example, the small noncoding RNAs and mRNA targets of Hfq, for which we combined chromosomal epitope tagging of the protein withsequencing the co-immunoprecipitated RNA. Current projects use Illuminasequencing to discover new RNA-binding proteins and the landscape of post-transcriptional regulations in bacteria and host. Furthermore, we want to developRNA deep sequencing as a robust tool to study―in parallel―the transcriptomesof bacterial pathogens and eukaryotic host over the course of infection, ideally atthe single-cell level.

RNA-protein interactions

Whereas there has been much progress on base pairing RNAs, theabundance and mechanisms of RNA molecules that target proteins to modulatetheir activity is little understood. For example, may RNA molecules serve totether virulence proteins until they are needed, or how many enzymes aretargeted by regulatory RNAs to fine-tune metabolism? We are using in vivo

cross-linking and RNA deep sequencing (CLIP-seq) to discover new RNA- binding proteins and map RNA-protein contacts in pathogenic bacteria. Theultimate goal is to understand how many proteins a regulatory RNA or even

mRNA “sees” from its birth to death, how many RNA-protein interactions there

29



are in the cell, how many of these are productive versus non-productive, andwhat the productive ones look like at the molecular level.

RNA localization

Contrary to previous beliefs, the bacterial cell contains complex structureswith many proteins, and indeed mRNAs, localized in distinct foci within thecell. An emerging focus of our research is to investigate the sub-cellular localization of sRNAs and other major components of the post-transcriptionalregulon in an attempt to decipher whether sRNAs are localized in distinctregions within the cell and determine how this localization may relate to thefunction of each sRNA.

MicroRNAs and Long Noncoding RNAs in infected eukaryotic hosts

Research over the last decade has implicated microRNAs in a plethora of eukaryotic disease-related pathways, including the mammalian immuneresponse, but surprisingly little remains known as to the microRNA response to

bacterial infections. Likewise, it is estimated that the human and mousegenomes express several hundred long noncoding RNA (lncRNA) molecules,with transcript lengths in the range of less than 1 to more than 100 kilobases.These lncRNA seem to play important roles in the epigenetic control of geneexpression and in organizing RNA-protein particles. We are investigating whichmicroRNAs and lncRNAs play a role in the response to infections by

Salmonella and other bacterial pathogens, again using systematic screeningapproaches followed by in-depth characterization of differentially expressedcandidate molecule. For example, we recently showed that the conserved Let-7microRNA family is down-regulated by bacterial LPS in mouse and humancells, and that this removes a post-transcriptional break on the IL-6 and IL-10cytokine mRNAs upon infection with Salmonella.

Jörgen Johansson17 think the key issue of new microbiology is Light anddark oscillations coordinate multicellular differentiation in Listeria coloniesthrough a blue-light receptor. And this issue of Listeria monocytogenes, a Gram-

positive bacterium frequently found in decaying soil, can occasionally causeserious life-threatening infections. Unlike many other bacteria, Listeriamonocytogenes is only motile at low temperatures (<30°C), due to a complexregulatory system preventing motility at higher temperatures. We show thatcolonies of Listeria monocytogenes undergo ring-formation (opaque andtranslucent rings) on agar plates in response to oscillating light/dark conditions.The ring formation is strictly dependent on a blue-light receptor, acting throughthe stress-sigma factor. Expression of the blue-light receptor is induced byH2O2 and a strain lacking Lmo0799 display a reduced survival at oxidative17 Umea University, Sweden

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stress. A saturated transposon mutant screening identified 65 differentgenes/operons required for ring-formation, mainly modulating activity inresponse to altered Reactive Oxygen Species (ROS) levels. Due to carbonlimitation, the bacteria from the inner part of the colony rapidly enter a resting

state, preventing translucent rings to form opaque rings when exposed to light.Our results show that night and day cycles coordinate a differentiation of aListeria colony, by a process requiring a blue-light receptor .

Jörgen Johansson attaches particular

importance to the biological reality

that diversify into multicellular

Listreria and the Control of virulence by small regulatory RNAs in the human

pathogen Listeria monocytogenes

Listeria monocytogenes is a gram- positive human pathogen causing

several different diseases, like meningitis,septicaemia and abortions. Listeria has an unique ability to cross the intestinal

barrier, the placental barrier and the blood-brain barrier during infection.

The bacteria is able to invade most tissues and shows a specific cell-infection

cycle (Figure 1).One characteristic of Listeria monocytogenes is its ability to polymerise the actin within the host in order to spread between cells (Figure 2)

During the last few years, it has become evident that all living organisms containsmall regulatory RNAs (sRNAs). These sRNAs affect diverse cellular functionssuch as transcription, translation, protein degradation, mRNA stability etc. RNAinterfence (RNAi) has arisen as a very versatile method to do functional knock-out mutants in eukaryotes and could prove important when curing diseases, suchas cancer.

In bacteria, sRNAs can function as antisense RNA (Figure 3) thereby affectingtranslation or inducing target mRNA degradation. They can also act by bindingspecific proteins and thereby sequester all such proteins.

31



Jörgen Johansson said my project involves the identification andcharacterisation of all sRNAs found in Listeria monocytogenes . The identifiedsRNAs will be knocked out and the phenotype of such mutants will becharacterised and my future work will especially focus on sRNAs involved in

virulence. I am planning to find the targets of these sRNAs by various methods,including in silico methods, transcriptome filters and 2D-gels. The mechanism by which the sRNAs function will be determined by different in vitro andgenetic techniques. Also, the function of the sRNAs at the different steps of Listeria infection will be determined

The Gram-positive bacterium Listeria monocytogenes uses a wide rangeof virulence factors for its pathogenesis. Expression of five of these factors has

previously been shown to be subjected to posttranscriptional regulation as aresult of their long 5´-untranslated region (5´-UTR). We have investigated the

presence of 5´-UTRs among the other known virulence genes and genes thatencode putatively virulence-associated surface proteins. Our results stronglysuggest that L. monocytogenes controls many of its virulence genes by amechanism that involves the 5´-UTR. These findings further emphasize theimportance of post-transcriptional control for L. monocytogenes virulence.

Dr Rotem Sorek 18 tink in the field Genomic probing into the immune

system of Bacteria are constantly exposed to phage attacks in the environment.

To survive these attacks, bacteria had developed multiple lines of molecular defense mechanisms such as restriction enzymes, abortive infectionmechanisms, and the adaptive immune system CRISPR. We have developedhigh throughput genomic tools to discover and characterize novel bacterialimmune systems that protect against phage. These methods, and the nature of the immune systems we detected, will be discussed in the talk.

I think the research scientists of the State of Israel give a hope and anabsolute guarantee for the future of their country. This is the case of the group of

Dr. Rotem Sorek researchers.

More than 2000 microbial genomes were sequenced to date, each of which containing ~3000 genes on average. But having the genome sequencealone does not mean that we understand the biology of an organism: about 50%of all genes in every newly sequenced species are of unknown function. Amongthe thousands of sequenced microbial genomes, millions of sequenced genes areso far uncharacterized.

18Dr. Rotem Sorek Office: Meyer Building, Room 210A Institute of Science, Department of Molecular Genetics, Israel

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Our lab is committed to develop innovative approaches that would allowelucidation of the novel biological functions "hiding" within uncharacterizedgenes. Current research directions in the lab include:

.

Fig 1. Increased drug resistance among pathogens versus reduced development of new drugs.A) Growing proportions of selected pathogens resistant against the antibiotic drug

ciprofloxacin. Similar increase in resistance was measured for most commonlyused antibiotics. B) The number of new antimicrobial drugs approved by theFDA between the years 1983-2007.

There is a growing need for new antimicrobial agents in the clinic. Drugresistance is spreading among pathogens, but the number of new antibiotics inthe market is constantly decreasing. As a result, hospital-acquired bacterialinfections now affect 1.7 million patients annually in the U.S. alone, and areresponsible for 99,000 deaths every year. There is, therefore, a clear and urgentneed to expand our clinical arsenal of antimicrobial drugs

We are developing a computational method that detects, among a large number

of microbial genomes, genes producing products that are toxic to bacteria. Thesegenes are tested for their antimicrobial activity. Our approach is based on a by-

product of the genome sequencing process, where initial assemblies invariablycontain gaps due to DNA fragments that cannot be cloned in bacteria (Fig 1).We discovered that these uncloneable gaps are caused by genes that are toxic toE. coli (Sorek et al., Science 2007). Thousands of such genes from hundreds of

bacteria were collected into the PanDaTox database. Among these toxic geneswe were able to discover new types of microbial toxins, new restrictionsenzymes, toxic small RNAs and toxic DNA binding motifs (Kimelman et al,

2012).

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http://www.ncbi.nlm.nih.gov/pubmed/17947550?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://www.weizmann.ac.il/pandatox

http://www.ncbi.nlm.nih.gov/pubmed/22300632


http://www.ncbi.nlm.nih.gov/pubmed/17947550?ordinalpos=3&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

http://www.weizmann.ac.il/pandatox





Fig. 2. Microbial genes discovered via our approach are toxic to E. coli. Shownare toxicity results for nine gap-residing genes tested and a control gene (Beta-galactosidase). The coding regions of these genes were cloned into E. coli under

the control of an inducible promoter system that is active only in the presence of IPTG. (A) Cells grown without the expression inducer IPTG; (B) grown with250uM IPTG; (C) with 800uM IPTG.

We are using the Illumina high-throughput sequencing platform to sequencewhole microbial genomes and transcriptomes. This technology generateshundreds of millions of short reads per run, reaching multiple giga bases of sequence per day. The Illumina technology enables us to study the evolution of

bacteria, discover phenotype altering mutations, and document dynamic

evolutionary processes.

Bacterial whole genome evolution

Using this technology, we documented processes of genome shrinkage in bacteria (Moran et al, Science 2009), and found how bacterial genomes evolvein response to phage attacks (Avrani et al, Nature 2011). We also developmethods for accurate detection of individual mutations in genomes using short-read sequencing technologies (Wurtzel et al, 2010).

RNA-mediated regulation in bacteria studied with RNA-seq

We employ RNA-seq to perform gene expression studies in bacteria and archaeaand to understand their complex transcriptomes. Although prokaryotictranscriptomes were considered simple until recently, RNA-seq studies nowrevolutionize our understanding of the complexity, plasticity and regulation of microbial transcriptomes (Sorek & Cossart, Nature Reviews Genetics 2010).

We know that two years ago To mark the 50th anniversary of the founding of

the Israeli Academy of Science and Humanity (Israel Academy of Sciences andHumanities), 17 presidents and heads of national science academies and

34

http://www.illumina.com/





http://www.illumina.com/







international around the world gathered in Jerusalem "to express their confidence and recognize the accomplishments of Israeli science." Theconference which took place during the "National Week of Science" whichmarked the anniversary of the birth of Albert Einstein, March 14.

The Israel Academy of Sciences and Humanities is a public research institutionlocated in Jerusalem. It brings together the best researchers in Israel in all fields:

Natural Sciences, Social Sciences and Humanities. Martin Buber, ScholemGershon Aaron Katzir and his first presidents were.

The purpose of the Academy is to promote scientific activity, to advise thegovernment in the research program and to represent Israeli science worldwide.International Conference of Presidents "Science and Responsibility" was held allweek in Jerusalem at the Israel Academy of Sciences with the participation of the State President Shimon Peres, the Knesset Speaker Reuven Rivlin and IsraeliMinister of Science, Prof. Daniel Hershkovitz.

Among the participants at this conference was attended by national leaders of the academies of science and scientists from countries and regions: Berlin-Brandenburg, China, Estonia, France, Germany, Great Britain, India, Japan,Poland, Sweden, Taiwan , USA and others.

Prominent Israeli public figures and members of the academies were present and

among them four Israelis Nobel Laureates: Professors Israel Aumann, AaronCiechanover, Avram Hershko and Ada Yonath. The President of the IsraelAcademy of Sciences, Professor Menahem Yaari, described the conference as amilestone in the development of international scientific relations of the State of Israel and an Israeli honor for science in the world.

The Academy of Science of Israel is celebrating its 50th was established in 1960at the initiative of Prime Minister Ben-Gurion, who also chaired the firstmeeting of the General Assembly of the Academy. Ratified by law in 1961, the

National Academy of Sciences has 98 academic scientists and the most eminentof Israel.

In June 1961, after a long preparation, the parliament voted in favor of legislation to govern the Academy. According to the latter, the main purpose of the Academy is to bring its members the best scientists in Israel, to advanceresearch of the natural sciences, to advise the government on scientific issues of national importance and represent the State before similar institutionsestablished abroad.

The Academy has two sections: one for Humanities and the Sciences of Nature.

35



The membership of each section is 35, not counting those who are aged 75;elected officials remain in the Academy member for life. The Academy meets atleast once a year for a general meeting, and each section meets three times ayear. The Academy President is appointed by the Head of State on the

recommendation of the Academy for a period of three years. Vice President of the Academy, is elected directly by members of the Academy for the sameduration.

Today the Academy continues his scientific work. The current president isProfessor Menahem Yaari of the Hebrew University of Jerusalem, and the VicePresident Professor Ruth Arnon of the Weizmann Institute in Rehovot. In thesection of the Humanities, a very important research work is done on the historyand development of Jewish liturgy and religious poetry. The Academy publisheswidely in almost all areas of science, but also in the field of Arts.

According to Professor Yaari: "The founding fathers considered theestablishment of the Academy of Sciences as representing the creation of acenter of knowledge and a scientific authority that can help the young state onmatters of scientific nature to implement . During the past 50 years, the state hasrarely helped the Academy, but recently it has been taking a significant share. "Professor Yaari reaffirms the desire to improve the knowledge base for decisionmakers, as long as they ask.

The President of the Israel Academy of Sciences, Professor Menahem Yaari,described the conference as "a milestone in the promotion of internationalscientific relations of the State of Israel and a tribute to the reputation of sciencein the Israeli world ". The Conference of Presidents focused on the responsibilityof researchers and scientific communities towards society on economic issues,health and progress of social welfare as well as the ethics of science and securityissues .

The event Jubilee began on March 14, the anniversary of Albert Einstein,celebrated in Israel as a National Day of Science. To celebrate this jubilee, a rareand unusual exhibition of original manuscripts of Albert Einstein's Theory of Relativity is presented to the Academy. A conference in memory of AlbertEinstein was given by the Nobel Prize in Physics French Claude Cohen-Tanoudji. The presidents and heads of Academies of Sciences were receivedTuesday, March 16 by the Scientific Committee of the Knesset. They were alsoreceived by the State President Shimon Peres during a reception for President.

The involvement of all stakeholders in the International Conference of Presidents reflects the importance of such a meeting, the highlight of all the

36



more informal appointments that take place regularly every year. Moreover, the presence of President Shimon Peres is a lot for the National Academy of Scienceof Israel.

For Steve Busby19 The last decade has seen a renaissance in the study of transcriptional regulation in Escherichia coli due mainly to the arrival of wholegenome sequences and detailed structural information about the multi-subunitRNA polymerase. Until recently, our knowledge was based on case-by-casestudies of favorite regulatory regions. However, the application of genomicmethodologies, such as transcriptomics, ChIP-on-chip and bioinformatics, hasrevealed new insights and unexpected complications. Promoters are the maindrivers of bacterial gene expression. Some recent results concerning theintegration of different signals at complex Escherichia coli promoters will be

presented.

Transcriptional regulation in bacteria

Steve Busby’s work concerns the mechanisms by which the expression of different genes is regulated in bacteria. Working with Escherichia coli K-12,over the past 25 years, the lab has elucidated some of the basic rules of promoter recognition by RNA polymerase and some of the fundamental mechanisms bywhich transcription activators function (see reviews listed below).

The work with RNA polymerase has focused on the roles of the alpha andsigma subunits, whilst the work on transcription activation has developed fromstudies of the cyclic AMP receptor protein (known as CRP or CAP), which haveestablished a paradigm for understanding transcription activation in bacteria.Early work with CRP, and with the related activator, FNR was concerned withsimple promoters, such as the E. coli lac or gal promoters, where one moleculeof activator is sufficient for full induction. Recently, the lab has turned itsattention to more complicated promoters that are regulated by many differentfactors. Because bacterial gene expression is exquisitely sensitive to theenvironment, the majority of promoters are complex and the lab has focused oncases where one molecule of activator is insufficient for full induction. 20

19Professor Steve Busby FRS Professor of Biochemistry Head of SchoolSchool of Biosciences University of

Birmingham, UK

20 Selected references Grainger, D, Lee, D & Busby, S (2009) Direct methods for studying transcription regulatory

proteins and RNA polymerase in bacteria. Current Opinion in Microbiology 12 531-535

Browning, D, Grainger, D & Busby S (2010) Effects of nucleoid-associated proteins on bacterial chromosome structure and gene expression. Current Opinion in Microbiology 13 773-780

Rossiter, A, Browning, D, Leyton, D, Johnson, M, Godfrey, R, Wardius, C, Desvaux, M, Cunningham, A, Ruiz-Perez, F, Nataro, J, Busby, S & Henderson, I (2011) Transcription of the plasmid-encoded toxin gene from enteroaggregative

Escherichia coli is regulated by a novel co-activation mechanism involving CRP and Fis. Molecular Microbiology 81 179-

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http://www.birmingham.ac.uk/schools/biosciences/index.aspx

http://www.birmingham.ac.uk/schools/biosciences/index.aspx



Stéphane Méresse21 working on Salmonella effector proteins in theregulation of host membrane trafficking. In other words Salmonella is a bacterial

pathogen. Ingested bacteria cross the intestinal epithelial barrier and proliferatewithin host cells. Intracellular replication takes place in a membrane-bound

compartment called the Salmonella-containing vacuole (SCV). Infected cells arecharacterized by a profound reorganisation of late endocytic compartments.While lysosomal contents (i.e. lysosomal enzymes) tend to disappear frominfected cells, lysosomal membrane glycoproteins (i.e. LAMP) accumulate onSCVs and on membrane tubular structures that extend from the SCV. Thesemodifications involve the translocation into the host cell of bacterial effector

proteins.Among these effector proteins, SifA is required for the SCV stability and

the formation of membrane tubular structures. Together with its eukaryotictarget SKIP, SifA is also necessary for the removal of kinesin-1, which isrecruited on the SCV membrane by the PipB2 effector.

We recently showed that the effector protein SopD2 is responsible for theSCV instability that triggers the cytoplasmic release of a sifA- bacterial mutant.Membrane tubular structures that extend from the SCV are the hallmark of Salmonella-infected cells, and until recently, these unique structures had not

been observed in the absence of SifA. The deletion of sopD2 in a sifA- mutantstrain re-established membrane trafficking from the SCV and led to theformation of new membrane tubular structures, the formation of which is

dependent on other Salmonella effector(s). Taken together, our data demonstratethat SopD2 inhibits the vesicular transport and the formation of tubules thatextend outward from the SCV and thereby contributes to the phenotypesobserved in absence of SifA.

The antagonistic roles played by SopD2 and SifA in the membranedynamics of the vacuole, and the complex actions of SopD2, SifA, PipB2 andother unidentified effector(s) in the biogenesis and maintenance of theSalmonella replicative niche will be discussed. The facultative intracellular

pathogen Salmonella enterica causes a variety of diseases, includinggastroenteritis and typhoid fever. Inside epithelial cells, Salmonella replicates invacuoles, which localize in the perinuclear area in close proximity to the Golgiapparatus. Among the effector proteins translocated by the Salmonella

pathogenicity island 2-encoded type III secretion system, SifA and SseG have been shown necessary but not sufficient to ensure the intracellular positioning of Salmonella vacuoles. Hence, we have investigated the involvement of other secreted effector proteins in this process. Here we show that SseF interacts

191

21 Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, case 906,13288 Marseille cedex 9

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functionally and physically with SseG but not SifA and is also required for the perinuclear localization of Salmonella vacuoles. The observations show that theintracellular positioning of Salmonella vacuoles is a complex phenomenonresulting from the combined action of several effector proteins.

Hélène Bierne22 made the presentation on Bacterial targeting of

chomatin : the Listeria paradigm. The facultative intracellular pathogenSalmonella enterica causes a variety of diseases, including gastroenteritis andtyphoid fever. Inside epithelial cells, Salmonella replicates in vacuoles, whichlocalize in the perinuclear area in close proximity to the Golgi apparatus.Among the effector proteins translocated by the Salmonella pathogenicity island2-encoded type III secretion system, SifA and SseG have been shown necessary

but not sufficient to ensure the intracellular positioning of Salmonella vacuoles.Hence, we have investigated the involvement of other secreted effector proteinsin this process. Here we show that SseF interacts functionally and physicallywith SseG but not SifA and is also required for the perinuclear localization of Salmonella vacuoles. The observations show that the intracellular positioning of Salmonella vacuoles is a complex phenomenon resulting from the combinedaction of several effector proteins.

In 2011 Researchers at the Pasteur Institute, INRA, INSERM and CNRShave identified a mechanism for the pathogenic bacterium Listeriamonocytogenes to his advantage to reprogram gene expression of the cell it

infects. L. monocytogenes secretes a protein that can penetrate the cell nucleusto take control of immune system genes of the host. This work has been

published on the website of the journal Science Jan. 20, 2011.

During infection, pathogenic bacteria must outwit the immune system of infected hosts to establish a sustainable way in his body. It was known

previously that control of the host immune system was through the manipulationof cellular signals responsible for the activation of immune cells. A study inListeria monocytogenes, the bacteria responsible for human listeriosis, comes

first to show that pathogenic bacteria can act directly in the nucleus of the hostcell, to their advantage to reprogram genes under the control of interferons, for activating the immune system (1). This study was conducted by Helen Biernewithin the unit of Bacteria-Cell Interactions (Institut Pasteur, Inserm Unit 604,INRA USC2020) directed by Pascale Cossart, in collaboration with other teamsfrom the Institut Pasteur, CNRS (Gif-sur-Yvette, University Paris Diderot - Paris7 and Grenoble) and IBMC (Porto).

This work is in line with a study by the same team in 2009. This allowed

22 INSTITUT PASTEURBacteria-cell interactions Unit – INSERM U604 – INRA USC2020Department of Cell biology and Infection 25 rue du Docteur Roux -75724 PARIS Cedex 15-France.

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the identification of a complex capable of locking gene expression bycompacting the DNA (2). Here, the researchers identified a small bacterial

protein, called LNTA, able to blow the lock by binding directly to the complex,causing the opening of the compacted DNA and thus access to genes.

It is unclear how, and when the bacteria decides to produce this factor LNTA, but its expression is fundamental to the success of infection with Listeria, whichcan enable or through it at will suppress immunity of the host.

These studies suggest the role of epigenetic regulation - changes in geneexpression that occur without alteration of the DNA sequence - in infection byL. monocytogenes. This discovery, if it held true for other pathogens, providevaluable information for understanding and ultimately better fight against theinfection and immunity.Dr Ali KILIC Paris 7 May 2012

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• Maynard Smith, J. (2000). “The concept of information in biology.” Philosophy of Science ,67(2): 177–194.

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the Biological Sciences including Medicine. Cambridge: Cambridge University Press.

Biology and PhilosophySpecial issue: Philosophy and the microbe (tentative titles; order tbc)

Philosophy of biology and philosophy of microbiology: What’s happening and

what’s next?

Maureen O’Malley (Sydney) and John Dupré (Exeter) Philosophy of microbiology from a microbiologist’s point of view

Ford Doolittle (Dalhousie) Microbes modeling ontogeny? Prospects and limitations

Alan Love (Minnesota) and Michael Travisano (Minnesota)

Philosophy of microbiology and pluralism: premature consensusCarol Cleland (Colorado @ Boulder)

43



Metaphysics of microbial consortia

Marc Ereshefsky (Calgary) and Makmiller Pedroso (Calgary) A process ontology of microbial activities

Eric Bapteste (UPMC, Paris) and John Dupré (Exeter) Microbial biodiversity as the fundamental biodiversity

Rob Knight and colleagues (Colorado @ Boulder) Extending biodiversity to microbes and beyond: the ‘lower-limit’ problem

Christophe Malaterre (IHPST, Paris) Beyond the genome: community-level analysis of the microbial world

Jack Gilbert (Argonne National Laboratory, Chicago)Contingency in microbial evolution and its consequences for philosophical

debates

Laura Franklin-Hall (NYU) Endosymbiosis and its ramifications for evolutionary theory

John Archibald (Dalhousie)Viruses, virology and their implications for philosophy of biology

Forest Rohwer (San Diego)The other eukaryotes: microbes that aren’t prokaryotes, and why philosophers

should be interested

Andrew Roger (Dalhousie), Maureen O’Malley (Sydney), Alastair Simpson(Dalhousie)What are fungi: a true kingdom with a boundary or an evolutionary

continuum?

Thomas Richards (Natural History Museum, London)

Selected Publications

Stern A., Mick E., Tirosh I., Sagy O., Sorek R.CRISPR targeting reveals a reservoir of common phages associated with the human gutmicrobiomeGenome Research, in press (2012). Dominissini D., Moshitch-Moshkovitz S., Schwartz S., Salmon-Divon M., Ungar L.,

Osenberg S., Cesarkas K., Jakob-Hirsch J., Amariglio N., Kupiec M., Sorek R., Rechavi G.Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq

Nature, in press (2012). Wurtzel O., Sesto N., Mellin J.R., Karunker I., Edelheit S., Becavin C., Archambaud C.,Cossart P., Sorek R.Comparative transcriptomics of pathogenic and non-pathogenic Listeria species

Molecular Systems Biology, in press (2012). Kimelman A., Levy A., Sberro H., Kidron S., Leavitt A., Amitai G., Yoder-Himes D.,Wurtzel O., Zhu Y., Rubin E.M., Sorek R.A vast collection of microbial genes that are toxic to bacteriaGenome Research, 22(4):802-9 (2012). Avrani S., Wurtzel O., Sharon I., Sorek R., Lindell D

Genomic island variability facilitates Prochlorococcus-virus coexistence Nature, 474(7353):604-608 (2011).

Sorek R., Cossart P.Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity.

Nature Reviews Genetics, 11(1):9-16 (2010).

44

http://www.weizmann.ac.il/molgen/Sorek/files/publications/Stern_GR_2012.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Dominissini_Nature_2012.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Wurtzel_MSB_2012.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Kimelman_GR_2012.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Avrani_Nature.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_NRG_2009.pdf











Moran N.A., McLaughlin H.J., Sorek R.The dynamics and timescale of ongoing genomic erosion in symbiotic bacteria.Science, 323(5912):379-382 (2009).Yoder-Himes D.R., Chain P.S.G., Zhu Y., Wurtzel O., Rubin E.M., Tiedje J.M., Sorek R.Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing.

PNAS , 106(10):3976-3981 (2009). Sorek R., Kunin V., Hugenholtz P.

CRISPR - a widespread anti-viral system that provides acquired resistance against viruses in prokaryotes. Nature Reviews Microbiology, 6(3):181-6 (2008).

Sorek R., Zhu Y., Creevey C., Francino M.P., Bork P., Rubin E.M.Genome-wide experimental determination of barriers to horizontal gene transfer.Science, 318(5855):1449-1452 (2007). Warnecke F., Luginbuhl P., Ivanova N., Ghassemian M., Richardson T.H., Stege J.T.,

Cayouette M., Djordjevic G., Aboushadi N., Sorek, R. et al.Metagenomic and functional analysis of hindgut microbiota of a wood feeding higher termite.

Nature, 450(7169):560-565 (2007). Shemesh R., Novik A., Edelheit S., Sorek R.

Genomic fossils as a snapshot of alternative splicing in the human transcriptome. PNAS , 103(5):1364-1369 (2006).

Sorek R., Lev-Maor G., Reznik M.*, Dagan T., Belinky F., Graur D., Ast G.Minimal conditions for exonization of intronic sequences: 5' splice site formation in aluexons.

Molecular Cell , 14(2): 221-231 (2004). Yelin R.*, Dahary D.*, Sorek R.*, Levanon E.Y., Goldstein O., Shoshan A., Diber A., Biton

S., Tamir Y., Khosravi R., Nemzer S., Pinner E., Walach S., Bernstein J., Savitsky K.,Rotman G.Widespread occurrence of antisense transcription in the human genome.

Nature Biotechnology, 21(4): 379-386 (2003).Lev-Maor G.*, Sorek R.*, Shomron N., Ast G.The birth of an alternatively spliced exon: 3' splice-site selection in Alu exons.Science, 300(5623): 1288-1291 (2003).Sorek R., Amitai M.

Piecing together the significance of splicing. Nature Biotechnology, 19(3): 196 (2001).

All Publications

Stern A., Mick E., Tirosh I., Sagy O., Sorek R.CRISPR targeting reveals a reservoir of common phages associated with the human gutmicrobiomeGenome Research, in press (2012). Dominissini D., Moshitch-Moshkovitz S., Schwartz S., Salmon-Divon M., Ungar L.,Osenberg S., Cesarkas K., Jakob-Hirsch J., Amariglio N., Kupiec M., Sorek R., Rechavi G.Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq

Nature, in press (2012). Wurtzel O., Sesto N., Mellin J.R., Karunker I., Edelheit S., Becavin C., Archambaud C.,

Cossart P., Sorek R.

45

http://www.weizmann.ac.il/molgen/Sorek/files/publications/MoranMcLaughlinSorek_Science_2009.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Yoder_Himes_PNAS_2009.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_et_al_Nature_Review_Microbiol_2008.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_el_al_Science_2007.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Warnecke_et_al_Nature_2007.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Shemesh_PNAS_2006.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_MolCell_2004.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Yelin_Nature_Biotech_2003.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Lev-Maor_Science_2003.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_2001.pdf























Comparative transcriptomics of pathogenic and non-pathogenic Listeria species Molecular Systems Biology, in press (2012). Amitai G., Sorek R.PanDaTox: a tool for accelerated metabolic engineering

Bioengineered Bugs, in press (2012).

Kimelman A., Levy A., Sberro H., Kidron S., Leavitt A., Amitai G., Yoder-Himes D.,Wurtzel O., Zhu Y., Rubin E.M., Sorek R.A vast collection of microbial genes that are toxic to bacteriaGenome Research, 22(4):802-9 (2012). Danan M., Schwartz S., Edelheit S., Sorek R.Transcriptome-wide discovery of circular RNAs in archaea

Nucleic Acids Research, 40(7):3131-42 (2012). Michaeli S., Doniger T., Gupta S.K., Wurtzel O., Romano M., Visnovezky D., Sorek R.,

Unger R., Ullu ERNA-seq analysis of small RNPs in Trypanosoma brucei reveals a rich repertoire of non-coding RNAs

Nucleic Acids Research, 40(3):1282-98 (2012). Sorek R., Serrano LBacterial genomes: from regulatory complexity to engineeringCurrent Opinion in Microbiology, 14:1-2 (2011). Avrani S., Wurtzel O., Sharon I., Sorek R., Lindell DGenomic island variability facilitates Prochlorococcus-virus coexistence

Nature, 474(7353):604-608 (2011). Stern A., Sorek R.The phage-host arms-race: Shaping the evolution of microbes.

BioEssays, 33(1):43-51 (2011). He S.*, Wurtzel O.*, Singh K., Froula J., Yilmaz S., Wang Z., Chen F., Lindquist E.A.,Sorek R., Hugenholtz P.Validation of two commercial ribosomal RNA removal methods for microbialmetatranscriptomics.

Nature Methods, 7:807-812 (2010). Wurtzel O., Dori-Bachash M., Pietrokovski S., Jurkevitch E., Sorek R.

Mutation detection with next-generation resequencing through a mediator genome. PLoS One, 5(12):e15628 (2010).

Stern A., Keren L., Wurtzel O., Amitai G., Sorek R.Self-targeting by CRISPR: gene regulation or autoimmunity?Trends in Genetics, 26(8):335-340 (2010).

Sorek R., Cossart P.Prokaryotic transcriptomics: a new view on regulation, physiology and pathogenicity. Nature Reviews Genetics, 11(1):9-16 (2010).

Wurtzel O., Sapra R., Chen F., Zhu Y., Simmons B., Sorek R.A single-base resolution map of an archaeal transcriptome.Genome Research, 20(1):133-41 (2010). Sorek R.When new exons are born

Heredity, 103:279–280 (2009). Yoder-Himes D.R., Chain P.S.G., Zhu Y., Wurtzel O., Rubin E.M., Tiedje J.M., Sorek R.Mapping the Burkholderia cenocepacia niche response via high-throughput sequencing.

PNAS , 106(10):3976-3981 (2009).

46




http://www.weizmann.ac.il/molgen/Sorek/files/publications/Amitai_BioengBugs_2012.pdf






http://www.weizmann.ac.il/molgen/Sorek/files/publications/Danan_NAR_2012.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Michaeli_NAR_2011.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_Curr_Opin_2011.pdf






http://www.weizmann.ac.il/molgen/Sorek/files/publications/Stern_Bioessays_2011.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/He_Wurtzel_Nature_Methods_2010.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Wurtzel_PLoS_One_2011.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Stern_TIG_2010.pdf






http://www.weizmann.ac.il/molgen/Sorek/files/publications/Wurtzel_GR_2009.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_2009_hdy.pdf























Moran N.A., McLaughlin H.J., Sorek R.The dynamics and timescale of ongoing genomic erosion in symbiotic bacteria.Science, 323(5912):379-382 (2009).Sorek R., Kunin V., Hugenholtz P.CRISPR - a widespread anti-viral system that provides acquired resistance against viruses in

prokaryotes Nature Reviews Microbiology, 6(3):181-6 (2008).

Sorek R., Zhu Y., Creevey C., Francino M.P., Bork P., Rubin E.M.Genome-wide experimental determination of barriers to horizontal gene transfer.Science, 318(5855):1449-1452 (2007). Warnecke F., Luginbuhl P., Ivanova N., Ghassemian M., Richardson T.H., Stege J.T.,

Cayouette M., Djordjevic G., Aboushadi N., Sorek, R. et al.Metagenomic and functional analysis of hindgut microbiota of a wood feeding higher termite.

Nature, 450(7169):560-565 (2007). Sorek R.

The birth of new exons: mechanisms and evolutionary consequences. RNA, 13(10):1603-1608 (2007).

Kunin V.*, Sorek R.*, Hugenholtz P.Evolutionary conservation of sequence and secondary structures in CRISPR repeats.Genome Biology, 8(4):R61 (2007).Lev-Maor G.*, Sorek R.*, Levanon E.Y., Paz N., Eisenberg E., Ast G.

RNA-editing mediated exon evolution.Genome Biology, 8(2):R29 (2007). Sorek R., Dror G., Shamir R.

Assessing the fraction of ancestral alternatively spliced exons in the human genome. BMC Genomics, 7:273(2006).

Shemesh R., Novik A., Edelheit S., Sorek R.Genomic fossils as a snapshot of alternative splicing in the human transcriptome.

PNAS , 103(5):1364-1369 (2006).Akiva P., Toporik A., Edelheit S., Peretz Y., Diber A., Shemesh R., Novik A., Sorek R.Transcription-mediated gene fusion in the human genome.Genome Research, 16(1):30-36 (2006).Dror G., Sorek R., Shamir R.

Accurate identification of alternatively spliced exons using support vector machine. Bioinformatics, 21(7): 897-901 (2005).

Eisenberg E., Nemzer S., Kinar Y., Sorek R., Rechavi G., Levanon E.Y.

Is abundant A-to-I RNA editing primate-specific?Trends in Genetics, 21(2):77-81 (2005). Neeman Y., Dahary D., Levanon E.Y., Sorek R., Eisenberg E.Is there any sense in antisense editing?Trends in Genetics, 21(10):544-547 (2005).Dahary D., Elroy-Stein O., Sorek R.

Naturally occurring antisense: Transcriptional leakage or real overlap?Genome Research, 15(3): 364-368 (2005). Lavorgna G., Dahary D., Lehner B., Sorek R., Sanderson C.M., Casari G.

In search of antisense.Trends in Biochemical Sciences, 29(2): 88-94 (2004).

47












http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_RNA_2007.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Kunin_Sorek_Hugen_Genome_Biol_2007.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Lev-Maor_Sorek_et_al_Genome_Biol_2007.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_et_al_BMC_Genomics_2006.pdf





http://www.weizmann.ac.il/molgen/Sorek/files/publications/Akiva_2006.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Dror_2005.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Eisenberg_2005_Trends-in-Genetics.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Neeman_2005_Trends-in-Genetics.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Dahary_2005.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Lavorgna_2004_Trends-in-Biochemical-Sciences.pdf




















Dagan T.*, Sorek R.*, Sharon E.*, Ast G., Graur D.AluGene: a database of Alu elements incorporated within protein-coding genes.

Nucleic Acids Research, 32: D489-D492 (2004).Sorek R., Shamir R., Ast G.How prevalent is functional alternative splicing in the human genome?

Trends in Genetics, 20(2): 68-71 (2004).Sorek R.*, Lev-Maor G.*, Reznik M.*, Dagan T., Belinky F., Graur D., Ast G.

Minimal conditions for exonization of intronic sequences: 5' splice site formation in aluexons.

Molecular Cell , 14(2): 221-231 (2004). Sorek R., Shemesh R., Cohen Y., Basechess O., Ast G., Shamir R.

A non-EST based method for exon-skipping prediction.Genome Research, 14(8): 1617-1623 (2004). Levanon E., Sorek R.

The importance of alternative splicing in the drug discovery process.Targets, 2(3): 109-114 (2003).

Hazkani-Covo E., Sorek R., Graur D.Evolutionary dynamics of large Numts in the human genome: rarity of independent insertionsand abundance of post-insertion duplications.

Journal of Molecular Evolution, 56(2): 169-174 (2003).Sorek R., Safer H.M.

A Novel method for computational identification of contaminated EST libraries. Nucleic Acids Research, 31(3): 1067-1074 (2003).

Yelin R., Dahary D., Sorek R., Levanon E.Y., Goldstein O., Shoshan A., Diber A., Biton S.,Tamir Y., Khosravi R., Nemzer S., Pinner E., Walach S., Bernstein J., Savitsky K., RotmanG.Widespread occurrence of antisense transcription in the human genome.

Nature Biotechnology, 21(4): 379-386 (2003).Lev-Maor G.*, Sorek R.*, Shomron N., Ast G.The birth of an alternatively spliced exon: 3' splice-site selection in Alu exons.Science, 300(5623): 1288-1291 (2003).Sorek R., Ast G.

Intronic sequences flanking alternatively spliced exons are conserved between human andmouse.Genome Research, 13(7): 1631-1637 (2003).Sorek R., Basechess O., Safer H.M.

Expressed sequence tags: clean before using.

Cancer Research, 63(20):6996 (2003). Sorek R., Ast G., Graur D.Alu containing exons are alternatively spliced.Genome Research, 12(7): 1060-1067 (2002). Sorek R., Amitai M.

Piecing together the significance of splicing. Nature Biotechnology, 19(3): 196 (2001).

http://www.weizmann.ac.il/molgen/Sorek/files/publications/Dagan_2004.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_2004_Trends-in-Genetics.pdf





http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_Genome_Res_2004.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Levanon_Targets_2003.pdf



http://www.weizmann.ac.il/molgen/Sorek/files/publications/Hazkani_Covo_2003.pdf


http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sorek_NAR_2003.pdf









http://www.weizmann.ac.il/molgen/Sorek/files/publications/Sore_Cancer_Res_2003.pdf






















Documents

On the Philosophy of New Microbiologys and the Biological Sciences (Jfb)