Nature Reviews Molecular Cell Biology http://www.nature.com/nrm/current_issue/ Nature Publishing Group en © 2008 Nature Publishing Group Nature Reviews Molecular Cell Biology 1471-0072 © 2008 Nature Publishing Group permissions@nature.com Nature Reviews Molecular Cell Biology http://www.nature.com/includes/rj_globnavimages/nrm_logo.gif http://www.nature.com/nrm/ The European Research Council — a new opportunity for European science http://dx.doi.org/10.1038/nrm2374 The long-awaited European Research Council (ERC), which receives money from the research budget of the European Union and will finance fundamental science for Europe's scientists, has finally been established. With a focus on excellence, calls for both young and experienced scientists and an average budget The European Research Council — a new opportunity for European science

Nature Reviews Molecular Cell Biology 9, 417 (2008). doi:10.1038/nrm2374

Author: Carl-Henrik Heldin

The long-awaited European Research Council (ERC), which receives money from the research budget of the European Union and will finance fundamental science for Europe's scientists, has finally been established. With a focus on excellence, calls for both young and experienced scientists and an average budget

]]> The European Research Council — a new opportunity for European science Carl-Henrik Heldin doi:10.1038/nrm2374 Nature Reviews Molecular Cell Biology 9, 417 (2008) Nature Reviews Molecular Cell Biology 9 5 Perspective 417 420 Paul Berg http://dx.doi.org/10.1038/nrm2385 Born in 1926, Paul Berg obtained his Ph.D. from Case Western Reserve University, Ohio, USA, and carried out postdoctoral studies with Herman Kalckar in Copenhagen, Denmark, and Arthur Kornberg at the National Institutes of Health and at Washington University, Missouri, USA. Berg joined the Department Paul Berg

Nature Reviews Molecular Cell Biology 9, 352 (2008). doi:10.1038/nrm2385

Author: Errol C. Friedberg

Born in 1926, Paul Berg obtained his Ph.D. from Case Western Reserve University, Ohio, USA, and carried out postdoctoral studies with Herman Kalckar in Copenhagen, Denmark, and Arthur Kornberg at the National Institutes of Health and at Washington University, Missouri, USA. Berg joined the Department

]]> Paul Berg Errol C. Friedberg doi:10.1038/nrm2385 Nature Reviews Molecular Cell Biology 9, 352 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 352 353 Mechanisms of asymmetric cell division: flies and worms pave the way http://dx.doi.org/10.1038/nrm2388 Asymmetric cell division is fundamental for generating diversity in multicellular organisms. The mechanisms that govern asymmetric cell division are increasingly well understood, owing notably to studies that were conducted in Drosophila melanogaster and Caenorhabditis elegans. Lessons learned from these two model organisms also Mechanisms of asymmetric cell division: flies and worms pave the way

Nature Reviews Molecular Cell Biology 9, 355 (2008). doi:10.1038/nrm2388

Author: Pierre Gönczy

Asymmetric cell division is fundamental for generating diversity in multicellular organisms. The mechanisms that govern asymmetric cell division are increasingly well understood, owing notably to studies that were conducted in Drosophila melanogaster and Caenorhabditis elegans. Lessons learned from these two model organisms also

]]> Mechanisms of asymmetric cell division: flies and worms pave the way Pierre Gönczy doi:10.1038/nrm2388 Nature Reviews Molecular Cell Biology 9, 355 (2008) Nature Reviews Molecular Cell Biology 9 5 Review 355 366 How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge http://dx.doi.org/10.1038/nrm2389 Biomedical research has never been more intellectually exciting or practically important to society. Ironically, pursuing a career as a biomedical scientist has never been more difficult. Here I provide unvarnished advice for young biomedical scientists on the difficulties that lie ahead and on how to How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge

Nature Reviews Molecular Cell Biology 9, 413 (2008). doi:10.1038/nrm2389

Author: Jonathan W. Yewdell

Biomedical research has never been more intellectually exciting or practically important to society. Ironically, pursuing a career as a biomedical scientist has never been more difficult. Here I provide unvarnished advice for young biomedical scientists on the difficulties that lie ahead and on how to

]]> How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge Jonathan W. Yewdell doi:10.1038/nrm2389 Nature Reviews Molecular Cell Biology 9, 413 (2008) Nature Reviews Molecular Cell Biology 9 5 Perspective 413 416 Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes http://dx.doi.org/10.1038/nrm2391 Acquired resistance to the action of insulin to stimulate glucose transport in skeletal muscle is associated with obesity and promotes the development of type 2 diabetes. In skeletal muscle, insulin resistance can result from high levels of circulating fatty acids that disrupt insulin signalling pathways. Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes

Nature Reviews Molecular Cell Biology 9, 367 (2008). doi:10.1038/nrm2391

Authors: Adilson Guilherme, Joseph V. Virbasius, Vishwajeet Puri & Michael P. Czech

Acquired resistance to the action of insulin to stimulate glucose transport in skeletal muscle is associated with obesity and promotes the development of type 2 diabetes. In skeletal muscle, insulin resistance can result from high levels of circulating fatty acids that disrupt insulin signalling pathways.

]]> Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes Adilson Guilherme Joseph V. Virbasius Vishwajeet Puri Michael P. Czech doi:10.1038/nrm2391 Nature Reviews Molecular Cell Biology 9, 367 (2008) Nature Reviews Molecular Cell Biology 9 5 Review 367 377 Chromosomes: Introducing HAC http://dx.doi.org/10.1038/nrm2392 Kinetochores are essential for proper chromosome segregation. The site of kinetochore assembly has been proposed to be controlled by epigenetic mechanisms; however, the chromatin 'signature' of human kinetochores has remained elusive. Nakano et al. now describe a novel human artificial chromosome (HAC) that allows Chromosomes: Introducing HAC

Nature Reviews Molecular Cell Biology 9, 351 (2008). doi:10.1038/nrm2392

Author: Francesca Cesari

Kinetochores are essential for proper chromosome segregation. The site of kinetochore assembly has been proposed to be controlled by epigenetic mechanisms; however, the chromatin 'signature' of human kinetochores has remained elusive. Nakano et al. now describe a novel human artificial chromosome (HAC) that allows

]]> Chromosomes: Introducing HAC Francesca Cesari doi:10.1038/nrm2392 Nature Reviews Molecular Cell Biology 9, 351 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 351 351 Expansion and evolution of cell death programmes http://dx.doi.org/10.1038/nrm2393 Cell death has historically been subdivided into regulated and unregulated mechanisms. Apoptosis, a form of regulated cell death, reflects a cell's decision to die in response to cues and is executed by intrinsic cellular machinery. Unregulated cell death (often called necrosis) is caused by overwhelming Expansion and evolution of cell death programmes

Nature Reviews Molecular Cell Biology 9, 378 (2008). doi:10.1038/nrm2393

Authors: Alexei Degterev & Junying Yuan

Cell death has historically been subdivided into regulated and unregulated mechanisms. Apoptosis, a form of regulated cell death, reflects a cell's decision to die in response to cues and is executed by intrinsic cellular machinery. Unregulated cell death (often called necrosis) is caused by overwhelming

]]> Expansion and evolution of cell death programmes Alexei Degterev Junying Yuan doi:10.1038/nrm2393 Nature Reviews Molecular Cell Biology 9, 378 (2008) Nature Reviews Molecular Cell Biology 9 5 Review 378 390 Non-hexameric DNA helicases and translocases: mechanisms and regulation http://dx.doi.org/10.1038/nrm2394 Helicases and nucleic acid translocases are motor proteins that have essential roles in nearly all aspects of nucleic acid metabolism, ranging from DNA replication to chromatin remodelling. Fuelled by the binding and hydrolysis of nucleoside triphosphates, helicases move along nucleic acid filaments and separate double-stranded Non-hexameric DNA helicases and translocases: mechanisms and regulation

Nature Reviews Molecular Cell Biology 9, 391 (2008). doi:10.1038/nrm2394

Authors: Timothy M. Lohman, Eric J. Tomko & Colin G. Wu

Helicases and nucleic acid translocases are motor proteins that have essential roles in nearly all aspects of nucleic acid metabolism, ranging from DNA replication to chromatin remodelling. Fuelled by the binding and hydrolysis of nucleoside triphosphates, helicases move along nucleic acid filaments and separate double-stranded

]]> Non-hexameric DNA helicases and translocases: mechanisms and regulation Timothy M. Lohman Eric J. Tomko Colin G. Wu doi:10.1038/nrm2394 Nature Reviews Molecular Cell Biology 9, 391 (2008) Nature Reviews Molecular Cell Biology 9 5 Review 391 401 Transcriptional control of human p53-regulated genes http://dx.doi.org/10.1038/nrm2395 The p53 protein regulates the transcription of many different genes in response to a wide variety of stress signals. Following DNA damage, p53 regulates key processes, including DNA repair, cell-cycle arrest, senescence and apoptosis, in order to suppress cancer. This Analysis article provides an overview Transcriptional control of human p53-regulated genes

Nature Reviews Molecular Cell Biology 9, 402 (2008). doi:10.1038/nrm2395

Authors: Todd Riley, Eduardo Sontag, Patricia Chen & Arnold Levine

The p53 protein regulates the transcription of many different genes in response to a wide variety of stress signals. Following DNA damage, p53 regulates key processes, including DNA repair, cell-cycle arrest, senescence and apoptosis, in order to suppress cancer. This Analysis article provides an overview

]]> Transcriptional control of human p53-regulated genes Todd Riley Eduardo Sontag Patricia Chen Arnold Levine doi:10.1038/nrm2395 Nature Reviews Molecular Cell Biology 9, 402 (2008) Nature Reviews Molecular Cell Biology 9 5 Analysis 402 412 Mechanisms of disease: Stress and disease connect at mTORC1 http://dx.doi.org/10.1038/nrm2396 Loss of the tuberous sclerosis complex (TSC) genes TSC1 and TSC2 leads to constitutive activation of the mammalian target of rapamycin complex-1 (mTORC1) and downstream signalling components, resulting in insulin resistance, the development of tumours and neurological disorders. Hotamisligil and colleagues now reveal Mechanisms of disease: Stress and disease connect at mTORC1

Nature Reviews Molecular Cell Biology 9, 349 (2008). doi:10.1038/nrm2396

Author: Ekat Kritikou

Loss of the tuberous sclerosis complex (TSC) genes TSC1 and TSC2 leads to constitutive activation of the mammalian target of rapamycin complex-1 (mTORC1) and downstream signalling components, resulting in insulin resistance, the development of tumours and neurological disorders. Hotamisligil and colleagues now reveal

]]> Mechanisms of disease: Stress and disease connect at mTORC1 Ekat Kritikou doi:10.1038/nrm2396 Nature Reviews Molecular Cell Biology 9, 349 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 349 349 Membrane trafficking: A maturing influence http://dx.doi.org/10.1038/nrm2397 Not only is the small GTPase RAB5 a key regulator of the early endocytic pathway, it has also been implicated in apoptotic cell engulfment, or phagocytosis. But the exact role of RAB5 in phagocytosis has so far remained uncharacterized.Using a fluorescence resonance energy Membrane trafficking: A maturing influence

Nature Reviews Molecular Cell Biology 9, 347 (2008). doi:10.1038/nrm2397

Author: Arianne Heinrichs

Not only is the small GTPase RAB5 a key regulator of the early endocytic pathway, it has also been implicated in apoptotic cell engulfment, or phagocytosis. But the exact role of RAB5 in phagocytosis has so far remained uncharacterized.Using a fluorescence resonance energy

]]> Membrane trafficking: A maturing influence Arianne Heinrichs doi:10.1038/nrm2397 Nature Reviews Molecular Cell Biology 9, 347 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 347 347 From the editors http://dx.doi.org/10.1038/nrm2398 As Jonathan W. Yewdell notes on page 413, “Biomedical research has never been more intellectually exciting or practically important to society. Ironically, pursuing a career as a biomedical scientist has never been more difficult”. Scientists at different stages in their careers can probably relate From the editors

Nature Reviews Molecular Cell Biology 9, 345 (2008). doi:10.1038/nrm2398

As Jonathan W. Yewdell notes on page 413, “Biomedical research has never been more intellectually exciting or practically important to society. Ironically, pursuing a career as a biomedical scientist has never been more difficult”. Scientists at different stages in their careers can probably relate

]]> From the editors doi:10.1038/nrm2398 Nature Reviews Molecular Cell Biology 9, 345 (2008) Nature Reviews Molecular Cell Biology 9 5 From The Editors 345 345 Membrane trafficking: Polar express http://dx.doi.org/10.1038/nrm2400 The vesicular coat protein clathrin is essential for endocytosis and cellular signalling processes at the plasma membrane. A new study in Nature uncovers an additional role for clathrin in intracellular trafficking and the maintenance of epithelial polarity.The establishment of epithelial cell polarity is Membrane trafficking: Polar express

Nature Reviews Molecular Cell Biology 9, 348 (2008). doi:10.1038/nrm2400

Author: Francesca Cesari

The vesicular coat protein clathrin is essential for endocytosis and cellular signalling processes at the plasma membrane. A new study in Nature uncovers an additional role for clathrin in intracellular trafficking and the maintenance of epithelial polarity.The establishment of epithelial cell polarity is

]]> Membrane trafficking: Polar express Francesca Cesari doi:10.1038/nrm2400 Nature Reviews Molecular Cell Biology 9, 348 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 348 349 Protein degradation: Ribophagy: selective ribosome 'eating' http://dx.doi.org/10.1038/nrm2401 Protein degradation by autophagy in yeast involves the sequestering of organelles and other macromolecular complexes within membrane vesicles, which are subsequently delivered to the vacuole where the cargo is degraded. Autophagy can occur through a basal, non-selective 'bulk' process or can involve an organelle-specific pathway. Protein degradation: Ribophagy: selective ribosome 'eating'

Nature Reviews Molecular Cell Biology 9, 348 (2008). doi:10.1038/nrm2401

Author: Arianne Heinrichs

Protein degradation by autophagy in yeast involves the sequestering of organelles and other macromolecular complexes within membrane vesicles, which are subsequently delivered to the vacuole where the cargo is degraded. Autophagy can occur through a basal, non-selective 'bulk' process or can involve an organelle-specific pathway.

]]> Protein degradation: Ribophagy: selective ribosome 'eating' Arianne Heinrichs doi:10.1038/nrm2401 Nature Reviews Molecular Cell Biology 9, 348 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 348 349 Protein translocation: Dancing the two-step with SAM http://dx.doi.org/10.1038/nrm2402 The outer membranes of mitochondria contain channel proteins with β-barrel structures. The precursors of β-barrel proteins are synthesized in the cytosol and are imported into mitochondria by the general translocase TOM and the sorting and assembly machinery (SAM) complex. But how β-barrel proteins are sorted Protein translocation: Dancing the two-step with SAM

Nature Reviews Molecular Cell Biology 9, 350 (2008). doi:10.1038/nrm2402

Author: Arianne Heinrichs

The outer membranes of mitochondria contain channel proteins with β-barrel structures. The precursors of β-barrel proteins are synthesized in the cytosol and are imported into mitochondria by the general translocase TOM and the sorting and assembly machinery (SAM) complex. But how β-barrel proteins are sorted

]]> Protein translocation: Dancing the two-step with SAM Arianne Heinrichs doi:10.1038/nrm2402 Nature Reviews Molecular Cell Biology 9, 350 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 350 350 In Brief http://dx.doi.org/10.1038/nrm2403 EpigeneticsRNA interference guides histone modification during the S phase of chromosomal replication.Kloc, A.et al. Curr. Biol.8 April 2008 (doi: 10.1016/j.cub.2008.03.016)How heterochromatin is inherited during the cell cycle is unknown. To examine this mechanism, Kloc et al In Brief

Nature Reviews Molecular Cell Biology 9, 347 (2008). doi:10.1038/nrm2403

EpigeneticsRNA interference guides histone modification during the S phase of chromosomal replication.Kloc, A.et al. Curr. Biol.8 April 2008 (doi: 10.1016/j.cub.2008.03.016)How heterochromatin is inherited during the cell cycle is unknown. To examine this mechanism, Kloc et al

]]> In Brief doi:10.1038/nrm2403 Nature Reviews Molecular Cell Biology 9, 347 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 347 347 Technology watch http://dx.doi.org/10.1038/nrm2404 Introducing BAC TransgeneomicsPoser et al. describe an efficient, generic and scalable approach to study protein function in mammalian cells based on bacterial artificial chromosome (BAC)-based transgenesis.Protein tagging in mammalian culture cells is typically done with cDNA-based transgenes that lack the normal non-coding Technology watch

Nature Reviews Molecular Cell Biology 9, 351 (2008). doi:10.1038/nrm2404

Introducing BAC TransgeneomicsPoser et al. describe an efficient, generic and scalable approach to study protein function in mammalian cells based on bacterial artificial chromosome (BAC)-based transgenesis.Protein tagging in mammalian culture cells is typically done with cDNA-based transgenes that lack the normal non-coding

]]> Technology watch doi:10.1038/nrm2404 Nature Reviews Molecular Cell Biology 9, 351 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 351 351 Cell migration: Group voyage http://dx.doi.org/10.1038/nrm2405 Collective cell movements — the movement of cells in clusters, strands, sheets and tubes — are a driving force in development, tissue repair and tumour metastasis. Despite the importance of these movements in both normal and pathological conditions, the molecular mechanisms that control them remain Cell migration: Group voyage

Nature Reviews Molecular Cell Biology 9, 346 (2008). doi:10.1038/nrm2405

Author: Ekat Kritikou

Collective cell movements — the movement of cells in clusters, strands, sheets and tubes — are a driving force in development, tissue repair and tumour metastasis. Despite the importance of these movements in both normal and pathological conditions, the molecular mechanisms that control them remain

]]> Cell migration: Group voyage Ekat Kritikou doi:10.1038/nrm2405 Nature Reviews Molecular Cell Biology 9, 346 (2008) Nature Reviews Molecular Cell Biology 9 5 Research Highlight 346 346