So, how can women be encouraged to apply for positions? One possible answer concerns female role models and the importance of mentor ing for younger scientists. Richard Henderson (MRC) r emarked that , in the UK, both Birkbeck College (London) and the Biochemistry depa r tmen t of Oxford Univers i ty have a t rad i t ion of employing female group leaders. Also, one only has to look to the te lomerase community, which is largely made up of highly successful female researchers , to appreciate the importance ofmentor ing. Most EU countries, as well as the USA and Canada, have some posit ive-action init iatives. However, these are general ly modest and include encouraging women to apply for fellowships, jobs and grants , and allocating a few gran ts or positions for women. Examples of these are the Dorothy Hodgkin Fel lowship Programme and the Danish F re j a Ini t ia t ive Gran t Programme, both of which selectively ta rge t women applicants . However, some delegates were wary of positive discrimination, especial ly at a higher level: 'we do more h a r m than good by ea rmark ing positions for women', r emarked Gasser. By contrast, Clut ter presented the flip side of the coin with the s t a tement ' i t ' s be t te r to be in a position of power than not to be in a position of power'.

Outlook The meeting succeeded in i ts aim to inform: the statistics presented spoke for themselves and underl ined the need for continued da ta collection and monitoring. Also, delegates were exposed to a wide range of ideas and init iat ives. This cross fert i l ization could be productive and several delegates left wi th the aim of promoting such projects in thei r own countries. EMBO itself was not excluded from this reform as Gannon commented tha t the gender composition of future EMBO meet ings and EMBO- sponsored lectures would be monitored. He also suggested tha t the European Molecular Biology Conference (EMBC; the body tha t funds EMBO) should consider running 'female-friendly' g ran t programmes; for example, fellowships for scientists returning after a career break. In addition, EMBO is drawing up a set of recommendations aimed at increasing female participation in the Life Sciences. These include insti tutions setting real is t ic ta rge ts regarding the number of women employed, offering men and women the same salar ies , budgets and laboratory space, and providing access to (and where applicable paying for) childcare. Despite the fact t ha t the female membership of the Royal Society of London (UK) has hovered between 2-4% for the pas t 50 years, there a re some hints of progress. For example,

over the pas t decade, there has been a s teady increase in the number of female professors employed. This could be the first ten ta t ive sign tha t the a tmosphere is changing and t ha t awareness-ra is ing and ini t ia t ives are working. However, we still have some way to go and steps need to be implemented to ensure tha t gender does not prevent scientists from par t ic ipat ing and succeeding in thei r endeavours.

References 1 Sciencepolicies in theEuropean Union.

Promoting excellence through mainstreaming gender equality. ETAN Expert Working Group on Women and Science

2 Wellcome Trust Unit for Policy Research in Science and Medicine (1997) Women andpeer- review: an audit of the Wellcome Trusts decision- making ongrants, London: Wellcome Trust

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

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

Emma K. Wilson Trends in Biochemical Sciences, Elsevier Science London, 84 Theobald's Road, London, UK WC1X 8RR. e-mail: tibs @ cu rrent-trends.com

This art icle was adapted, with permission, from Trends in B i o ch em i ca l Sc iences 26, No. 9, pp. 526-528 (2001).

[ Book Review

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 0471 415383

Conventional in vi tro

reconsti tut ion approaches used to invest igate the mechanisms of DNA and RNA production and processing are founded on the assumpt ion tha t

the requisi te complexes can be eluted from the cell nucleus in a soluble form. The original in vi tro reconst i tut ion of RNA polymerase II and II I t ranscr ip t ion supported this principle 1.

In reviewing over twenty years of biochemical fract ionation studies, Peter Cook challenges, in a new book ent i t led Pr inc ip l e s o f N u c l e a r S t r u c t u r e a n d

F u n c t i o n , the assumpt ion tha t active complexes can be extracted from nuclei. In prompt ing the s tudent to reflect upon this paradox, the book might serve an impor tan t role in teaching critical th inking skills to emerging nuclear biochemists and molecular biologists.

The book provides a very good overview of the underlying biochemistry of the major processes acting on the genome (replication, t ranscr ip t ion and repair). However, the biochemistry is presented in, what for many, will be an entirely new light. Cook elegantly ini t ia tes the s tudent in th inking about the physical, chemical and topological

requi rements for the biochemical reactions by t rans la t ing molar i ty into mean three-dimensional distr ibutions. After expanding on the topological requi rements for t ranscr ip t ion within cells, he challenges the strict t rans la t ion o f in v i tro reconst i tut ion exper iments to mechanisms of action in vivo.

Centra l to his discussion of nuclear biochemistry is a provocative, but controversial, hypothesis - tha t RNA and DNA polymerases function in the organizat ion of the genome in both in te rphase and mitosis. Classic papers produced dur ing the 1980s from the Cook group 2,3 form the basis of this hypothesis and represen t serious challenges to the conventional view tha t RNA and DNA polymerases are the mobile components of the elongation process. To argue his point, Cook points out t ha t the topology of t ranscr ip t ion intui t ively favours moving the chromat in r a the r than the polymerase and elongat ing t ranscr ipt . For the reader

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to critically evaluate the hypothesis , I felt t ha t the exemplary t ransmiss ion electron microscopy studies on in s i tu RNA polymerase II t ranscr ip t ion of the Balbiani r ing genes by the Danehol t group should have been included. These studies appear to support the existence of mobile po]ymerases and loop domains in vivo.

Being static images, however, they cannot in themselves define wha t the mobile and immobile components are.

The book is not, nor is i t in tended to be, a s tand-alone resource on nuclear s t ructure in the classical sense of the word. With the exception of the nucleolus, classical nuclear s tructures, such as PML bodies, Cajal (coiled) bodies, in terchromat in granule clusters and per ichromat in fibrils, receive litt le at tent ion. This deficiency is par t icu la r ly evident for in terchromat in granule clusters. There is an extensive body of fluorescence and t ransmiss ion electron microscopy examining the role of this s t ructure in pre-mRNA splicing and trafficking. In this light, the book only par t ia l ly succeeds in introducing the re la t ionship between nuclear archi tecture and nuclear function.

Rather than introduce s tudents to classical s t ructures of the cell nucleus and the i r puta t ive functions, the author chose to examine u l t r a s t ruc tu ra l work p r imar i ly performed within his own research group. The most significant of these studies, wi th respect to introducing nuclear s t ructure morphologically, is thick embedment-free sections of nuclei p repared by a novel electroelution s t ra tegy uti l izing physiological buffers 4. This s tudy demonst ra ted an in termedia te- f i lament- l ike network anas tamatos ing throughout the nucleus. The other s t ructures examined in this book, ' t ranscr ip t ion factories' in part icular , are much less well defined from a classical-morphology perspective. The amorphous bodies embedded wi thin the 'nucleoskeleton' of th ick sections or u ran ium-cont ras ted thin sections are of l imited value in introducing classical nuclear u l t ras t ructure .

The objective of the book, however, is achieved by i l lus t ra t ing the re la t ionship between DNA and RNA polymerase activi ty and nuclear organization. The ut i l i ty of this text is i ts discussion of the biochemistry in a s t ructura l l ight and not as a classical introduction for someone in teres ted specifically in the cell biology of the nucleus. To compensate for these

l imitations, an online web resource page is associated with the book. The reader can easily find excellent sources for the missing classical cell biology by referr ing to addit ional web ]inks associated with each chapter. Clearly, this is for the more enthusiast ic s tudent , bu t i t does provide an excellent supplementary resource for those in teres ted in designing an undergradua te course ut i l iz ing this book for both content and structure.

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

References 1 Dignam, J.D. et al. (I983)Accurate transcription

initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11,1475-1489

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

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

4 Jackson, D.A. and Cook, P.R. (t988)Visualization of a filamentous nncleoskeleton with a 23 nm axial repeat. EMBO J. 7, 3667-3677

From tadpoles to TIMPs - making the most of M M P s

Matrix Metalloproteinase Protocols (Methods in Molecular Biology) Edited by lan M. Clark, Humana Press, 2001. $135.00 (545 Pages) ISBN 0 89603 733 9

Matr ix metal]oproteases (MMPs) first h i t the scene in 1962 when the enzymatic act ivi ty associated with tadpole ta i l resorpt ion was shown to be tha t of a collagenase 1. While quite a few

labs made s teady progress on unders tanding the biology of these enzymes and their endogenous inhibi tors (the ' t issue inhibi tors ofmeta l loproteases ' or TIMPs), the MMPs real ly came to prominence in the ear ly 1980s when they were implicated in tumor cell invasion and

metas tas i s 2. Since then, the MMPs have become a major drug ta rge t for pharmaceut ica l companies wi th programs in oncology and in a r th r i t i s / rheumat i sm, al though the first drug with metal loprotease inhibi tory act ivi ty to be approved for use is for per iodontal disease ( 'Periostat ' , Collagenex Pharmaceut ica ls , Newtown, PA, USA). Not surprisingly, all this a t tent ion from pharmaceut ica l companies has coincided with a large increase in the number of labs wi th an in teres t in MMPs or thei r inhibitors.

Today, MMP researchers come from disciplines as diverse as developmental biology, clinical medicine and p lan t biology, meaning tha t a book such as Matr ix Metalloproteinase Protocols should have a large readership. The editor, I an M. Clark, has done an excellent job in pu t t ing together a collection of art icles t ha t span what is now a fair ly wide field. He has clearly divided the book into four different sections. The first is a general overview containing six essays tha t serve to orient the reader in various aspects of MMP biology. These detai led reviews come with extensive lists of references and will be useful to both novice and es tabl i shed researcher alike. Given the speed at which this field is expanding, reviews run the danger of being out of date before they are published, but, a l though ment ion of the most recent ly described MMPs is miss ing here, the content and wri t ing are of a high s t andard and will be informative despi te the publicat ion lag. In Chap te r 3, covering s t ruc tura l studies and contr ibuted by Wolfram Bode and Klaus Maskos, the authors point out the absence of specific discussions of three-dimensional s t ructures amongst the p le thora of general reviews on MMPs and TIMPs. Tbeir contribution expert ly fills t ha t void.

The second section deals wi th expression and purification of MMPs and TIMPs. Together, these chapters cover prokaryotic and a range of eukaryot ic expression systems. Par t icu la r ly impressive is Chapter 14 on 'Purif icat ion of MMPs and TIMPs', contr ibuted by Kenlchi Shimokawa and Hideaki Nagase. The very detai led 'Notes' section at the end of this chapter should make MMP and TIMP purification e lementary for even the confirmed non-biochemist. Indeed, the 'Notes' section, a t the end of each chapter, is where the benefit of much, often hard- earned, experience is to be reaped and is a valuable addit ion in a lmost every case.

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