So, how can women be encouraged to applyfor positions? One possible answer concernsfemale role models and the importance ofmentoring for younger scientists. RichardHenderson (MRC) remarked that, in theUK, both Birkbeck College (London) and theBiochemistry department of OxfordUniversity have a tradition of employingfemale group leaders. Also, one only has tolook to the telomerase community, whichis largely made up of highly successfulfemale researchers, to appreciate theimportance of mentoring. Most EUcountries, as well as the USA and Canada,have some positive-action initiatives.However, these are generally modest andinclude encouraging women to apply forfellowships, jobs and grants, andallocating a few grants or positions forwomen. Examples of these are theDorothy Hodgkin Fellowship Programmeand the Danish Freja Initiative GrantProgramme, both of which selectivelytarget women applicants. However, somedelegates were wary of positivediscrimination, especially at a higherlevel: ‘we do more harm than good byearmarking positions for women’,remarked Gasser. By contrast, Clutterpresented the flip side of the coin with thestatement ‘it’s better to be in a position ofpower than not to be in a position of power’.

Outlook

The meeting succeeded in its aim to inform:the statistics presented spoke for themselvesand underlined the need for continued datacollection and monitoring. Also, delegateswere exposed to a wide range of ideas andinitiatives. This cross fertilization could beproductive and several delegates left withthe aim of promoting such projects in theirown countries. EMBO itself was notexcluded from this reform as Gannoncommented that the gender composition offuture EMBO meetings and EMBO-sponsored lectures would be monitored. Healso suggested that the European MolecularBiology Conference (EMBC; the body thatfunds EMBO) should consider running‘female-friendly’grant programmes; forexample, fellowships for scientists returningafter a career break. In addition, EMBO isdrawing up a set of recommendations aimedat increasing female participation in the LifeSciences. These include institutions settingrealistic targets regarding the number ofwomen employed, offering men and womenthe same salaries, budgets and laboratoryspace, and providing access to (and whereapplicable paying for) childcare. Despitethe fact that the female membership of theRoyal Society of London (UK) has hoveredbetween 2–4% for the past 50 years, thereare some hints of progress. For example,

over the past decade, there has been asteady increase in the number of femaleprofessors employed. This could be thefirst tentative sign that the atmosphere ischanging and that awareness-raising andinitiatives are working. However, we stillhave some way to go and steps need to beimplemented to ensure that gender doesnot prevent scientists from participatingand succeeding in their endeavours.

References

1 Science policies in the European Union.Promoting excellence through mainstreaminggender equality. ETAN Expert Working Group onWomen and Science

2 Wellcome Trust Unit for Policy Research inScience and Medicine (1997) Women and peer-review: an audit of the Wellcome Trusts decision-making on grants, London: Wellcome Trust

3 Wenneras, C. and Wold, A. (1997) Nepotism andsexism in peer-review. Nature 347, 341–343

4 Grant, J. et al. (1997) No evidence of sexism inpeer-review. Nature 390–438

Emma K. Wilson

Trends in Biochemical Sciences, ElsevierScience London, 84 Theobald’s Road,London, UK WC1X 8RR.e-mail: tibs@current-trends.com

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The cell nucleus –

ending the conspiracy

of silence

Principles of Nuclear Structure and

Function

By Peter R. Cook, 2001, Wiley–Liss.£57.50/$79.95 (352 pages) ISBN 0 471 41538 3

Conventional in vitroreconstitutionapproaches usedto investigate themechanisms ofDNA and RNAproduction andprocessing arefounded on theassumption that

the requisite complexes can be eluted fromthe cell nucleus in a soluble form. Theoriginal in vitro reconstitution of RNApolymerase II and III transcriptionsupported this principle1.

In reviewing over twenty years ofbiochemical fractionation studies, PeterCook challenges, in a new book entitledPrinciples of Nuclear Structure andFunction, the assumption that activecomplexes can be extracted from nuclei. Inprompting the student to reflect upon thisparadox, the book might serve animportant role in teaching criticalthinking skills to emerging nuclearbiochemists and molecular biologists.

The book provides a very good overviewof the underlying biochemistry of the majorprocesses acting on the genome (replication,transcription and repair). However, thebiochemistry is presented in, what for many,will be an entirely new light. Cook elegantlyinitiates the student in thinking about thephysical, chemical and topological

requirements for the biochemicalreactions by translating molarity intomean three-dimensional distributions.After expanding on the topologicalrequirements for transcription withincells, he challenges the strict translationof in vitro reconstitution experiments tomechanisms of action in vivo.

Central to his discussion of nuclearbiochemistry is a provocative, butcontroversial, hypothesis – that RNA andDNA polymerases function in theorganization of the genome in bothinterphase and mitosis. Classic papersproduced during the 1980s from the Cookgroup2,3 form the basis of this hypothesisand represent serious challenges to theconventional view that RNA and DNApolymerases are the mobile components ofthe elongation process. To argue his point,Cook points out that the topology oftranscription intuitively favours movingthe chromatin rather than the polymeraseand elongating transcript. For the reader

Book Review

This article was adapted, with permission,from Trends in Biochemical Sciences 26,No. 9, pp. 526–528 (2001).

to critically evaluate the hypothesis, I feltthat the exemplary transmission electronmicroscopy studies on in situ RNApolymerase II transcription of theBalbiani ring genes by the Daneholt groupshould have been included. These studiesappear to support the existence of mobilepolymerases and loop domains in vivo.Being static images, however, they cannotin themselves define what the mobile andimmobile components are.

The book is not, nor is it intended to be,a stand-alone resource on nuclearstructure in the classical sense of theword. With the exception of the nucleolus,classical nuclear structures, such as PMLbodies, Cajal (coiled) bodies,interchromatin granule clusters andperichromatin fibrils, receive littleattention. This deficiency is particularlyevident for interchromatin granuleclusters. There is an extensive body offluorescence and transmission electronmicroscopy examining the role of thisstructure in pre-mRNA splicing andtrafficking. In this light, the book onlypartially succeeds in introducing therelationship between nuclear architectureand nuclear function.

Rather than introduce students toclassical structures of the cell nucleus andtheir putative functions, the author choseto examine ultrastructural work primarilyperformed within his own research group.The most significant of these studies, withrespect to introducing nuclear structuremorphologically, is thick embedment-freesections of nuclei prepared by a novelelectroelution strategy utilizingphysiological buffers4. This studydemonstrated an intermediate-filament-like network anastamatosing throughoutthe nucleus. The other structuresexamined in this book, ‘transcriptionfactories’ in particular, are much less welldefined from a classical-morphologyperspective. The amorphous bodiesembedded within the ‘nucleoskeleton’ofthick sections or uranium-contrasted thinsections are of limited value in introducingclassical nuclear ultrastructure.

The objective of the book, however, isachieved by illustrating the relationshipbetween DNA and RNA polymeraseactivity and nuclear organization. Theutility of this text is its discussion of thebiochemistry in a structural light and notas a classical introduction for someoneinterested specifically in the cell biology ofthe nucleus. To compensate for these

limitations, an online web resource page isassociated with the book. The reader caneasily find excellent sources for themissing classical cell biology by referringto additional web links associated witheach chapter. Clearly, this is for the moreenthusiastic student, but it does providean excellent supplementary resource forthose interested in designing anundergraduate course utilizing this bookfor both content and structure.

Michael J. Hendzel

Dept of Oncology and Cross CancerInstitute, University of Alberta, 11560University Ave., Edmonton, Alberta, Canada T6G 1Z2.e-mail: michaelh@cancerboard.ab.ca

References

1 Dignam, J.D. et al. (1983) Accurate transcriptioninitiation by RNA polymerase II in a solubleextract from isolated mammalian nuclei. NucleicAcids Res. 11, 1475–1489

2 Jackson, D.A. and Cook, P.R. (1985) Transcriptionoccurs at a nucleoskeleton. EMBO J. 4, 919–925

3 Jackson, D.A. and Cook, P.R. (1986) Replicationoccurs at a nucleoskeleton. EMBO J. 5, 1403–1410

4 Jackson, D.A. and Cook, P.R. (1988) Visualizationof a filamentous nucleoskeleton with a 23 nmaxial repeat. EMBO J. 7, 3667–3677

From tadpoles to TIMPs

– making the most of

MMPs

Matrix Metalloproteinase Protocols

(Methods in Molecular Biology)

Edited by Ian M. Clark, Humana Press, 2001.$135.00 (545 Pages) ISBN 0 89603 733 9

Matrixmetalloproteases(MMPs) first hitthe scene in 1962when theenzymatic activityassociated withtadpole tailresorption wasshown to be that ofa collagenase1.While quite a few

labs made steady progress onunderstanding the biology of theseenzymes and their endogenous inhibitors(the ‘tissue inhibitors of metalloproteases’or TIMPs), the MMPs really came toprominence in the early 1980s when theywere implicated in tumor cell invasion and

metastasis2. Since then, the MMPs havebecome a major drug target forpharmaceutical companies with programsin oncology and in arthritis/rheumatism,although the first drug withmetalloprotease inhibitory activity to beapproved for use is for periodontal disease(‘Periostat’, Collagenex Pharmaceuticals,Newtown, PA, USA). Not surprisingly, allthis attention from pharmaceuticalcompanies has coincided with a largeincrease in the number of labs with aninterest in MMPs or their inhibitors.

Today, MMP researchers come fromdisciplines as diverse as developmentalbiology, clinical medicine and plantbiology, meaning that a book such asMatrix Metalloproteinase Protocols shouldhave a large readership. The editor, Ian M.Clark, has done an excellent job in puttingtogether a collection of articles that spanwhat is now a fairly wide field. He hasclearly divided the book into four differentsections. The first is a general overviewcontaining six essays that serve to orientthe reader in various aspects of MMPbiology. These detailed reviews come withextensive lists of references and will beuseful to both novice and establishedresearcher alike. Given the speed at whichthis field is expanding, reviews run thedanger of being out of date before they arepublished, but, although mention of themost recently described MMPs is missinghere, the content and writing are of a highstandard and will be informative despitethe publication lag. In Chapter 3, coveringstructural studies and contributed byWolfram Bode and Klaus Maskos, theauthors point out the absence of specificdiscussions of three-dimensionalstructures amongst the plethora ofgeneral reviews on MMPs and TIMPs.Their contribution expertly fills that void.

The second section deals withexpression and purification of MMPs andTIMPs. Together, these chapters coverprokaryotic and a range of eukaryoticexpression systems. Particularlyimpressive is Chapter 14 on ‘Purificationof MMPs and TIMPs’, contributed by Kenichi Shimokawa and Hideaki Nagase.The very detailed ‘Notes’ section at the endof this chapter should make MMP andTIMP purification elementary for even theconfirmed non-biochemist. Indeed, the‘Notes’ section, at the end of each chapter,is where the benefit of much, often hard-earned, experience is to be reaped and is avaluable addition in almost every case.

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