a lilliputian cooperator

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TRENDS in Genetics Vol.17 No.6 June 2001 316 News & Comment http://tig.trends.com 0168–9525/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved. In Brief Stem cells from fat The shortage of stem cells could now be avoided by transforming fat cells harvested by liposuction into stem cells. A collaborative effort between scientists at UCLA and the University of Pittsburgh shows that the fat cells can be transformed into muscle, bone and cartilage cells, previously possible only by using stem cells derived from bone marrow, brain or fetal tissue. The use of fetal tissue for stem-cell research has already initiated a heated debate on its ethical implications. Fat cells would provide a plentiful and economical alternative that could be used for replacing dead or injured tissue at various sites in the body. [Zuk, P.A. et al. (2001) Tissue Eng. 7, 211–228] AP The Janus Serum Bank: forward thinking allows retrospective analysis Named after the two-faced Roman god, the Janus Serum Bank symbolizes the possibility of looking for the causes of disease both retrospectively and prospectively. This vital biomedical resource was highlighted in a recent JAMA publication that linked Chlamydia trachomatis serotype and cervical squamous cell carcinoma [Anttila, T. et al. (2001) JAMA 285, 47–51]. Under the control of the Norwegian Cancer Society, the bank consists of 600 000 serum samples obtained from 300 000 Norwegians during medical examinations and when donating blood. Most individuals have a time-course of sera in the bank (up to 12 samples). The Janus project currently cooperates with groups from Scandinavia, the UK, Germany, the US and Australia. Researchers can obtain between 500 to 3000 samples for projects; each sample from a patient comes with three healthy age- and sex-matched controls. The samples are coded for anonymity and the experiments are done ‘blind’ – which samples are from controls and which from patients are only revealed once the results are in. Full details about the project and how to apply for samples are given on the Norweigan Cancer Societies website (http://www.kreft.no/forhelsepersonell/ janusserumbank/english/). SG A missense mutation associated with schizophrenia Schizophrenia is a complex heterogeneous syndrome, involving both environmental and genetic factors. Although a familial subtype of catatonic schizophrenia is transmitted in an autosomal dominant manner, the gene responsible has eluded scientists. Recently, however, a German group led by K.P. Lesch spotted a missense mutation that co-segregates with the familial catatonia. Studying the human chromosome 22 in a large pedigree, the researchers used genetic linkage analysis followed by positional cloning to find the mutation. The new gene, named WKL1, is expressed only in the nervous system, not in other peripheral areas. The protein encoded by the WKL1 gene is similar to ion channels, and structural analysis shows that the protein conformation changes following mutation – indicating a molecular mechanism for the pathogenesis of this disease. [Meyer, J. et al. (2001) Mol. Psychiatry 6, 302–306] MP A Lilliputian cooperator Organs and organisms grow until they reach their appointed size – and then they stop. But what tells them to stop? Why are our arms shorter than our legs, for instance? Ernst Hafen and colleagues at the University of Zurich are seeking regulators that link growth and differentiation. They identified the Lilliputian gene (lilli) in Drosophila that could be at the convergence of patterning mechanisms and pathways that regulate growth during development. In the developing Drosophila eye, the Ras signaling pathway controls growth, survival and differentiation by different thresholds of MAP-kinase activity. Lilli cooperates with the Ras/MAP-kinase pathway in cell-fate specification in the developing eye. However, loss of Lilli also leads to a reduction of cell and organ size. The gene encodes a nuclear protein related to the AF4/FMR2 family. In humans, mutations affecting these genes are associated with diseases such as mental retardation and acute lymphoblastic leukemia. [Wittwer, F. et al. (2001) Development 128, 791–800; Halfar, K. et al. (2001) Development 128, 1687–1696]. PL Mining Medline It’s every child’s dream – a machine that does your homework for you. Edward Marcotte and colleagues at the University of Texas and UCLA have programmed their computer to read the 12 million Medline abstracts and find the ones they’re looking for. Their approach scores the abstracts on the comparative overuse of certain ‘discriminating words’. The group’s research focuses on building up networks of interacting proteins in yeast. Given the choice between doing thousands of experiments and mining the available information, they preferred the latter. Marcotte says, ‘It’s the lazy man’s approach to finding protein interactions.’ Despite his modesty, the program has had lots of interest from other scientists keen to use it in their research. It has also allowed a rapid expansion of the Database of Interacting Proteins, curated by collaborator loannis Xenarios, and will speed up the construction of other databases, such as SwissProt, where evaluation of the literature is normally the rate-limiting step. [Marcotte, E.M. et al. (2001) Bioinformatics 17, 359–363] HD PartsList: a structural genomics resource A valuable new resource called PartsList was recently announced. Based on an essential protein structure, the protein fold, the idea behind the project is to use a ‘ranking’ comparison system. The approximately 420 known folds can be ranked on the basis of more than

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Page 1: A Lilliputian cooperator

TRENDS in Genetics Vol.17 No.6 June 2001316 News&Comment

http://tig.trends.com 0168–9525/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.

In Brief

Stem cells from fatThe shortage of stem cells could now beavoided by transforming fat cells harvestedby liposuction into stem cells. Acollaborative effort between scientists atUCLA and the University of Pittsburghshows that the fat cells can be transformedinto muscle, bone and cartilage cells,previously possible only by using stem cellsderived from bone marrow, brain or fetaltissue. The use of fetal tissue for stem-cellresearch has already initiated a heateddebate on its ethical implications. Fat cellswould provide a plentiful and economicalalternative that could be used for replacingdead or injured tissue at various sites in thebody. [Zuk, P.A. et al. (2001) Tissue Eng.7, 211–228] AP

The Janus Serum Bank:forward thinking allowsretrospective analysisNamed after the two-faced Roman god, theJanus Serum Bank symbolizes thepossibility of looking for the causes ofdisease both retrospectively andprospectively. This vital biomedicalresource was highlighted in a recent JAMApublication that linked Chlamydiatrachomatis serotype and cervicalsquamous cell carcinoma [Anttila, T. et al.(2001) JAMA 285, 47–51]. Under the control of the Norwegian Cancer Society,the bank consists of 600 000 serumsamples obtained from 300 000Norwegians during medical examinationsand when donating blood. Mostindividuals have a time-course of sera inthe bank (up to 12 samples). The Janusproject currently cooperates with groupsfrom Scandinavia, the UK, Germany, theUS and Australia. Researchers can obtainbetween 500 to 3000 samples for projects;each sample from a patient comes withthree healthy age- and sex-matchedcontrols. The samples are coded foranonymity and the experiments are done‘blind’ – which samples are from controlsand which from patients are only revealedonce the results are in. Full details aboutthe project and how to apply for samplesare given on the Norweigan CancerSocieties website(http://www.kreft.no/forhelsepersonell/janusserumbank/english/). SG

A missense mutationassociated with schizophrenia

Schizophrenia is a complex heterogeneoussyndrome, involving both environmentaland genetic factors. Although a familialsubtype of catatonic schizophrenia istransmitted in an autosomal dominantmanner, the gene responsible has eludedscientists. Recently, however, a Germangroup led by K.P. Lesch spotted a missensemutation that co-segregates with thefamilial catatonia.

Studying the human chromosome 22 in a large pedigree, the researchers usedgenetic linkage analysis followed bypositional cloning to find the mutation. The new gene, named WKL1, is expressedonly in the nervous system, not in otherperipheral areas. The protein encoded bythe WKL1 gene is similar to ion channels,and structural analysis shows that theprotein conformation changes followingmutation – indicating a molecularmechanism for the pathogenesis of thisdisease. [Meyer, J. et al. (2001) Mol.Psychiatry 6, 302–306] MP

A Lilliputian cooperatorOrgans and organisms grow until theyreach their appointed size – and then theystop. But what tells them to stop? Why areour arms shorter than our legs, for instance?Ernst Hafen and colleagues at the Universityof Zurich are seeking regulators that linkgrowth and differentiation. They identifiedthe Lilliputian gene (lilli) in Drosophila thatcould be at the convergence of patterningmechanisms and pathways that regulate

growth during development. In thedeveloping Drosophila eye, the Rassignaling pathway controls growth, survivaland differentiation by different thresholds of MAP-kinase activity. Lilli cooperates with the Ras/MAP-kinase pathway in cell-fate specification in the developing eye. However, loss of Lilli also leads to areduction of cell and organ size. The geneencodes a nuclear protein related to theAF4/FMR2 family. In humans, mutationsaffecting these genes are associated withdiseases such as mental retardation andacute lymphoblastic leukemia. [Wittwer, F.et al. (2001) Development 128, 791–800;Halfar, K. et al. (2001) Development 128,1687–1696]. PL

Mining MedlineIt’s every child’s dream – a machine thatdoes your homework for you. EdwardMarcotte and colleagues at the University ofTexas and UCLA have programmed theircomputer to read the 12 million Medlineabstracts and find the ones they’re lookingfor. Their approach scores the abstracts onthe comparative overuse of certain‘discriminating words’. The group’sresearch focuses on building up networks of interacting proteins in yeast. Given thechoice between doing thousands ofexperiments and mining the availableinformation, they preferred the latter.Marcotte says, ‘It’s the lazy man’s approachto finding protein interactions.’ Despite hismodesty, the program has had lots ofinterest from other scientists keen to use itin their research. It has also allowed a rapidexpansion of the Database of InteractingProteins, curated by collaborator loannisXenarios, and will speed up theconstruction of other databases, such asSwissProt, where evaluation of theliterature is normally the rate-limiting step. [Marcotte, E.M. et al. (2001) Bioinformatics17, 359–363] HD

PartsList: a structuralgenomics resourceA valuable new resource called PartsListwas recently announced. Based on anessential protein structure, the protein fold,the idea behind the project is to use a ‘ranking’ comparison system. Theapproximately 420 known folds can be ranked on the basis of more than