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Select Research Group Head Prof. Sir Tom Blundell Prof. Kevin Brindle Dr Bill Broadhurst Dr Guy Brown Dr Mark Carrington Prof. Paul Dupree Prof. Gerard Evan - Head of Dept Prof. Richard Farndale Dr Giorgio Favrin Dr Jenny Gallop Dr Nick Gay Dr Andrew Grace Dr Jules Griffin Dr Brian Hendrich Dr Andrew Hesketh Dr Robin Hesketh Dr Matt Higgins Dr Florian Hollfelder Dr Hee-Jeon Hong Prof. Chris Howe Dr Marko Hyvonen Prof. Steve Jackson Dr Tony Jackson Prof. Richard Jackson Prof. Ernest Laue Prof. Peter Leadlay Dr Kathryn Lilley Dr Karen Lipkow Dr Rick Livesey Prof. Ben Luisi Dr Sarah Lummis Dr Juan Mata Dr John McCafferty Prof. Jim Metcalfe Dr Masanori Mishima Dr Eric Miska Dr Tom Monie Dr Helen Mott Dr Natasha Murzina Dr Daniel Nietlispach Dr Darerca Owen Prof. Steve Oliver Dr Luca Pellegrini Dr Markus Ralser Dr Nick Robinson Prof. George Salmond Dr Deirdre Scadden Dr José Silva Prof. Austin Smith Prof. Chris Smith Dr Nancy Standart Prof. Dame Jean Thomas Dr Aviva Tolkovsky Dr Martin Welch Dr Joyce Wong Dr Nianshu Zhang

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Select by Subject or Manager DNA Sequencing Facility . . . . . Mr John Lester _______________________________ Quantitative Proteomics . . . . . Dr Kathryn Lilley _______________________________ Proteomics Core Services . . . . . Dr Mike Deery _______________________________ Protein & Nucleic Acid Chemistry . . . . . Dr Len Packman _______________________________ Metabolomics . . . . . Dr Jules Griffin _______________________________ Baculovirus Facility . . . . . Dr Darerca Owen _______________________________ Biophysics Facility . . . . . Dr Katherine Stott _______________________________ Crystallographic X-ray Facility . . . . . Dr Dima Chirgadze _______________________________ NMR spectroscopy . . . . . Dr Daniel Nietlispach _______________________________ Fermentation Facility . . . . . Dr Nianshu Zhang _______________________________ Bioinformatics & Computational Biology Services . . . . . Dr Jenny Barna _______________________________ Computer & IT Support . . . . . Dr Erik Timmers _______________________________

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Select past member of Department Dr Stephen Bell Prof. Jonathan Blackburn Dr David Brown Dr Pak-Lee Chau Dr Hal Dixon (deceased) Dr Jessica Downs Prof. David Ellar Dr Paul Kemp Dr Simon Lovell Dr Kenji Mizuguchi Dr Massimo Paoli Prof. Richard Perham Dr Peter Reynolds Dr Philip Rubery Dr Gerry Smith Dr Margaret Sunde Prof. Jamie Vandenberg Dr Kira Weissman

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Neocortical stem and progenitor cell biology

Research Groupings: Developmental and regenerative biology and medicine | Functional genomics, systems biology and genetic medicine

Migrating neurons (green, GFP-expressing) in a neocortical slice culture.	Subcellular distribution of a GFP-tagged form of a novel FGF signaling inhibitor, expressed in fibroblasts.

A fundamental question in neural stem cell biology is how particular classes of neurons are generated at specific places and times in the nervous system in order for them to be incorporated correctly into neuronal circuits. We study this question in a region of the developing forebrain, the neocortex. The neocortex is the part of the brain that integrates sensations, executes decisions and is responsible for cognition and perception. Neurons in the cortex are organized in two ways: they belong to one of six layers of neurons, each of which is generated in a stereotyped order, and they belong to a discrete piece or area of the cortex that is dedicated to a single function such as visual processing or motor control. All of the neurons in the cortex are generated from a population of multipotent neocortical stem and progenitor cells. The majority of the research in the lab centers on the biology of neocortical stem cells and in particular how neocortical stem cells produce layer-specific neurons in order (the timing problem) and for the correct area (the patterning problem). Our current work on the patterning problem is focused two strands: how diffusible extracellular signals control neocortical stem and progenitor cell positional identity, one readout of which is a transcription factor-based map that controls spatial identity; and how this map is then used to produce spatially discrete populations of neurons. To do so, we combine in vivo location analysis by chromatin-IP (ChIP-on-chip) to identify the target genes of each transcription factor with expression profiling following gain and loss of function analyses of each factor and bioinformatics to produce predictive models of stem and progenitor cell decision making.
How neurons for specific layers are generated in order is a timing problem, in that it is controlled by a poorly understood cellular mechanism intrinsic to neocortical stem cells. Our work in this area concentrates on testing candidate genes and mechanisms for controlling developmental timing in neocortical stem cells in vivo. Finally, the lab is also studying some of the clinical consequences of our research, particularly in the aetiology and pathogenesis of autistic spectrum conditions.

Binding curves of a neocortical transcription factor to the promoters of four target genes in neocortical stem cells, as detected in ChIP-on-chip experiments. Peaks indicate bound regions of each promoter.

Lab members
Jessica M Alsio, Grace Nisbet, Stephen Sansoml

References