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PERSPECTIVES a reaction–diffusion mechanism. I attribute 10-YEAR ANNIVERSARY SERIES — VIEWPOINT this concept to Eric Karsenti, who mooted the idea in the mid 1980s for signals dif- A decade of molecular cell biology: fusing away from DNA in eggs. However, it wasn’t proven until the development of fluorescence resonance energy transfer achievements and challenges (FRET)-based activity biosensors in the past decade2,3. In general, fluorescence sensors Asifa Akhtar, Elaine Fuchs, Tim Mitchison, Reuben J. Shaw, Daniel St Johnston, of biochemical activity are a very important Andreas Strasser, Susan Taylor, Claire Walczak and Marino Zerial development. Abstract | Nature Reviews Molecular Cell Biology celebrated its 10‑year anniversary Reuben J. Shaw. One area close to our own during this past year with a series of specially commissioned articles. work is the unexpected re-emergence of To complement this, here we have asked researchers from across the field for their metabolism and its relationship to growth insights into how molecular cell biology research has evolved during this past control and cancer. Advances in autophagy decade, the key concepts that have emerged and the most promising interfaces continue to amaze me in terms of how little basic information we actually have on how a that have developed. Their comments highlight the broad impact that particular cell works. Autophagy regulators are highly advances have had, some of the basic understanding that we still require, and the conserved proteins in a central cell biologi- collaborative approaches that will be essential for driving the field forward. cal process that is deregulated in common human diseases, yet much of the biochemi- cal framework for this process has been What do you feel have been the Takahashi were paradigm-shifting. Their decoded only recently. Other newly decoded most significant, and perhaps most work reported the creation of induced pluri- central regulators and processes, ranging surprising, new concepts to emerge in potent stem (iPS) cells from mouse skin from cilia to sirtuins, microRNAs (miRNA­s) molecular cell biology during the past decade? fibroblasts when cultured in embryonic stem and pathways such as those involving Has this progress been enabled by a particular cell (ESC) conditions1. It was remarkable Hippo and mammalian target of rapamycin technical advance? that transient over­expression of a mere four (mTOR), underlying so much biology, have transcription factors, OCT4, SOX2, MYC changed half of what we know. These are Asifa Akhtar. There have been a number and Krüppel-like factor 4 (KLF4) — all natu- very exciting times. of important concepts that have emerged. rally expressed by ESCs — could achieve One that particularly jumps to mind is the this dramatic dedifferentiation of fibroblasts. Daniel St Johnston. Several surprising importance of epigenetics in gene regulation. This finding has allowed researchers to concepts have emerged during the past The field of epigenetics has flourished over derive patient-tailored iPS cells to study the decade: first, the amazing extent to which the past 10 years. It is clear that chromatin biology of a host of different human diseases basic cell biological processes have been provides an ideal platform for various post- — a first step, but a major one, for the future conserved during the evolution of eukary- translational modifications on DNA and development of new drugs and treatments otes; second, how much gene regulation is histones, which act as a signalling platfor­m in medicine. post-transcriptional, particularly through for various cellular processes. I also think small non-coding RNAs; third, how basic that the discovery that a combination of Tim Mitchison. Reaction–diffusion gradi­ cellular processes, such as endocytic traffick- four transcription factors can induce a pluri­ ent­s specifying positional information ing, microtubule dynamics or mitochondrial potent state was phenomenal and has stimu­­ inside cells. Gradients of signalling mol­ behaviour are modulated during the course lated a lot of research in the stem cell field1. ecules were long known in developmental of normal development; and last, the wide Last, but not least, the involvement of non- biology and paracrine physiology. But range of cell biological and developmental coding RNAs in various cellular and nuclear gradients inside cells being used as a spa- events that are regulated in response to processes is totally fascinating. The mecha- tial organizing system is a new concept. cell­ular stresses, such as DNA damage or nisms by which long non-coding RNAs Bicoid, a classic developmental morphogen,­ nutrien­t deprivation, and how these are used regulate gene expression await excitin­g diff­uses inside a syncytium, but this is a as signals during normal development. discoverie­s in the coming years. special case. Gradients of RAN•GTP from The most important technical advances mitotic chromatin and of Aurora B activity have been high-throughput sequencing, Elaine Fuchs. For the stem cell field, there from chromatin in M phase and midzones in which has provided the complete sequence of is no question that the findings of Shinya cytokinesis are classic cellular signals that we many genomes, and the use of RNA interfer- Yamanaka and his co-worker Kazutoshi now know organize space inside cells using ence (RNAi) to knock down gene function. NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 12 | OCTOBER 2011 | 669 © 2011 Macmillan Publishers Limited. All rights reserved PERSPECTIVES The contributors* Asifa Akhtar obtained her bachelors degree in biology at University (PAR) proteins control the organization of the cytoskeleton, and how College London (UCL), UK, in 1993 and her Ph.D. in 1998 at the Imperial mRNAs are targeted to the correct positions within the cell. Cancer Research Fund in London, studying transcription regulation in Andreas Strasser is Joint Head of the Molecular Genetics of Cancer Division Richard Treisman’s laboratory. She continued in the field of chromatin at The Walter and Eliza Hall Institute of Medical Research in Melbourne, regulation as a postdoctoral fellow at the European Molecular Biology Australia. His research is focused on programmed cell death and how Laboratory (EMBL), Heidelberg, Germany, and the Adolf Butenandt defects in this process cause cancer or autoimmune disease and affect the Institute, Munich, Germany, in Peter Becker’s laboratory until 2001. response of tumour cells to anticancer therapy. Key discoveries have been: From 2001, she led her own research as a Group Leader at the EMBL. that abnormalities in cell death control can cause cancer or autoimmune In 2009, her laboratory moved to the Max Planck Institute of disease; that B cell lymphoma 2 (BCL‑2) and death receptors regulate Immunobiology and Epigenetics, Freiburg, Germany. Her laboratory distinct pathways to apoptosis; the pro-apoptotic BCL‑2 homology 3 primarily studies chromatin and epigenetic mechanisms, especially (BH3)-only proteins and that they are essential for initiation of programmed focusing on the regulation of the X chromosome by the phenomenon of cell death; that BCL‑2‑interacting mediator of cell death (BIM; also known dosage compensation in Drosophila melanogaster. In 2008, she received as BCL‑2L11) is required for negative selection of autoreactive thymocytes the European Life Science Organization (ELSO) award for significant and mature T cells; and that p53 upregulated modulator of apoptosis contribution in the field. (PUMA; also known as BBC3) and NOXA (also known as PMAIP1) are Elaine Fuchs is the Rebecca Lancefield Professor in Mammalian Cell essential for DNA damage-induced apoptosis mediated by the tumour Biology and Development at The Rockefeller University, New York, USA, suppressor p53. Current efforts include the development of antagonists and an investigator of the Howard Hughes Medical Institute (HHMI). of pro-survival proteins for cancer therapy. She has published >260 scientific papers and is internationally known Susan Taylor is an HHMI investigator at the University of California, for her research in the biology of skin stem cells and their role in normal San Diego (UCSD), USA, in the Departments of Pharmacology and tissue development and cancer. She is a member of the National Chemistry and Biochemistry. She received her Ph.D. in physiological Academy of Sciences, USA, and a foreign associate of the European chemistry from The Johns Hopkins University, Baltimore, Maryland, USA, Molecular Biology Organization (EMBO). Her honours include the working with Edward Heath. For her postdoctoral research, she worked first US National Medal of Science, the L’Oreal-UNESCO Award for with Brian Hartley at the Medical Research Council Laboratory of Molecular Women in Science and the Albany Medical Center Prize in Medicine Biology in Cambridge, UK, and then with Nathan Kaplan at UCSD. and Biomedical Research (shared with Shinya Yamanaka and James Her research focuses on the structure and function of protein kinases, in Thompson). She is immediate Past President of the International particular on cyclic AMP-dependent protein kinases, which serve as a Society for Stem Cell Research. prototype for the large protein kinase superfamily. She merges biophysics Tim Mitchison obtained a biochemistry degree at Oxford University, UK, and structural biology with cell biology and imaging to study not only the and then moved to the laboratory of Marc Kirschner for his Ph.D. thesis, structures of the protein kinase A

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