果冻影院

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Glial cell development听and plasticity

Principal Investigator: Professor William D. Richardson, FLS, FMedSci FRS
ORCID iD:

Oligodendrocyte plasticity and its role in learning and memory. Pools of precursor/ stem cells persist in the adult CNS.听

Some inhabit the subventricular zones (SVZ) of the forebrain where they produce new neurons for the olfactory bulb throughout life. Others reside in the hippocampus and continuously generate new hippocampal interneurons in the adult.听

Another population of neural precursor cells - adult oligodendrocyte precursors (OLPs, also known as OPCs or NG2 glia) - is scattered uniformly throughout the adult brain and spinal cord.听

We showed that NG2 glia continue to divide and generate new myelin-forming oligodendrocytes throughout adulthood in mice.听

What is the physiological role of these late-born oligodendrocytes and the myelin they produce?

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One important function of adult-born oligodendrocytes is to repair demyelinating damage following CNS injury or disease.

Our lab has shown that they also play a critical role in learning and memory formation in normal healthy mice. For example, production of new OLs is necessary for adult mice to learn new motor skills (e.g. running on a wheel with unevenly spaced rungs), or to improve their cognitive performance in a radial maze task that taxes working memory.

Working memory is a short-term, low-capacity memory system that is important for all sorts of mental tasks such as decision-making or problem solving.听In humans, working memory is tightly correlated with measures of general or "fluid" intelligence. Thus, plasticity of OL lineage cells and myelin is central to learning, memory and cognitive performance.

PDFs of Richardson lab publications

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Neuro-glia development and disease

Principal Investigator: Professor Nicoletta Kessaris
ORCiD ID:听

Brain development commences in the embryo and continues well into postnatal stages as neurons and glia assume their final positions, before undergoing maturation, apoptosis, or maintaining a stem-cell-like state.

Disruptions to these developmental processes can give rise to brain disturbances and neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD), which initiate early in life but become apparent during childhood.

Our laboratory is committed to unravelling the genetic underpinnings of forebrain neuron and glia development to understand how developmental abnormalities may contribute to NDDs.

We explore the impact of genetic mutations on the generation, specification, and maturation of neurons and glia in the forebrain, as well as the formation of cortical neuronal networks and behaviours associated with NDDs.

Employing model organisms, our research utilizes a diverse set of approaches, including in vivo loss- and gain-of-function genetic approaches, -omic technologies, electrophysiology, and behavioural analysis.

Our overarching goal is to decipher how genetics and the environment influence brain formation, ultimately shedding light on the origins and behavioural manifestations of ASD and NDDs.

Cellular and molecular neuroscience

Principal Investigator: Professor Huiliang Li
ORCiD ID:听

The Central Nervous System (CNS) is made up of diverse types of neurons and glial cells.听Glia (literally 'glue') have proven to be much more than a passive support matrix for neurons. In fact, mounting evidence indicates that glia are highly complex cells engaged in a plethora of brain activities.

Employing transgenic approaches, we aim to find answers to the following questions:

• How do Neural Stem Cells (NSCs) choose glial versus neuronal fate?听
• What are the molecular mechanisms behind gliogenesis?
• What are the causes and consequences of glial dysfunction?

We are also investigating the impact of cholesterol metabolism in both healthy and diseased brains. The brain is known to have a higher cholesterol concentration (15鈥�20 mg/g tissue) than other tissues (2 mg/g tissue on average). Cholesterol is unable to cross intact blood brain barrier (BBB) and has its metabolic machinery to regulate homeostasis.

Our research interests include:

• The effects of disturbances in brain cholesterol homeostasis on autism spectrum disorder (ASD), Alzheimer鈥檚 disease (AD) and aged brains.
• The regulation of the gut-microbiota-brain axis on cholesterol metabolism in ASD, AD, and aged brains.
• The regulation of the liver-brain axis on cholesterol metabolism in ASD, AD, and aged brains.

Glial cells in neural circuits

Principal Investigator: Dr Matthew Swire
ORCiD ID:听

In the vertebrate brain and spinal cord, cells called "oligodendrocytes" construct an insulating layer around "axons" - long filamentous extensions of "neurons", the electrically excitable cells. This insulation, "myelin", greatly speeds up the electrical signals sent by neurons as well as providing energetic support to neurons and their axons.

Recently it has been demonstrated that oligodendrocytes and the myelin that they make also help the brain to adapt to new experiences, contributing to learning and memory formation. How exactly myelin influences learning is still not well understood.

One hypothesis is that oligodendrocytes can sense the neurons that are activated by specific behaviours, resulting in the formation or remodelling of myelin on those active neurons. We predict that this process will fine-tune electrical signals and alter the connectivity of the active neurons leading to the development of new neuronal circuits responsible for new behaviours.

Using a range of transgenic mice, we aim to determine:

• How the myelin on activated neurons changes during learning
• The mechanisms that may enable oligodendrocytes to sense neuronal activity
• How changes to myelination alters neuronal connectivity.

The Neural Development, Repair and Plasticity Group

Glial cell development, plasticity & function

Neuro-glia development & disease

Mechanisms of neural development

Oligodendrocyte development & myelination

PhD Student

PhD Student

PhD Student

PhD Student

Alexander Fudge
Technician / PhD Student

Dr Cheng Yang
Associate Staff

Visiting PhD Student

Marcus Lloyd
Research Assistant

Lab Manager

Selected Publications

Funding and Partnerships

Grants awarded:

William Richardson (since 2013)

• 2019-2024: Wellcome Trust Investigator Award 鈥淎daptive myelination in learning and memory鈥�
• 2019-2024: Sanming collaborative project (with H. Li, J. Wood, J. Zhao, M. H盲usser, D. Attwell at 果冻影院 and others at Sun Yat-sen University, Shenzhen, China)
• 2019-2023: BBSRC Research Grant 鈥淐ontrol of oligodendrocyte development by OLIG2 and chromatin remodelling complexes鈥� (with H. Li, WIBR)
• 2015-2022: Wellcome Strategic award 鈥淔unctional Neuromics of the Cerebral Cortex鈥� [with K. Harris, M. H盲usser, M. Carandini, N. Kessaris (果冻影院), P. Somogyi (Oxford U), J. Hjerling-Leffler, M. Nilsson, S. Linnarsson (Karolinska Inst, Sweden)]
• 2013-2019: Wellcome Trust Senior Investigator Award, "Transcriptional control of CNS myelination in development and maturity"
• 2012-2017: European Research Council Advanced Grant "MOTOGLIA: axoglial synapses, adult myelination and motor skills learning"
• 2008-2013: National Institutes of Health "Cellular and genetic origins of astrocytes" (with David Rowitch, UCSF; Charles D Stiles, Harvard Med Sch; Ben Barres, Stanford U)
• 2008-2013: Medical Research Council Programme "Stem and progenitor cells of the postnatal CNS" (with Nicoletta Kessaris, WIBR)

Nicoletta Kessaris

• 2015-2022: Wellcome Strategic award 鈥淔unctional Neuromics of the Cerebral Cortex鈥� [with K. Harris, M. H盲usser, M. Carandini, W. Richardson (果冻影院), P. Somogyi (Oxford U), J. Hjerling-Leffler, M. Nilsson, S. Linnarsson (Karolinska Inst, Sweden)]
• 2016-2020: BBSRC project grant, 鈥淟HX6, MTG8 and MTG16: functions and interactions in cortical interneuron development鈥�
• 2017-2018: PTEN Foundation project grant 鈥淭he impact of the PTENR173C point-mutation on neuronal development in mice and explanted neurons鈥� (with B. Vanhaesebroeck, 果冻影院)
• 2010-2013: Wellcome project grant, 鈥淥ptogenetic manipulation of interneuron development and function鈥� (with D. Kullmann and M.K. H盲usser, 果冻影院)
• 2008-2014: European Research Council Starting Independent Research Grant, 鈥淢igration and integration of GABAergic interneurons into the developing cerebral cortex: a transgenic approach鈥�
• 2008-2011: Wellcome Trust PhD studentship, 鈥淣eurogenesis in the mouse telencephalon鈥�
• 2008-2013: Medical Research Council Programme "Stem and progenitor cells of the postnatal CNS" (with W. Richardson (PI), WIBR)
• 2007-2012: Wellcome Programme grant, 鈥淒iversity and function of CNS glia: a transgenic and electrophysiological approach鈥� (with W. Richardson (PI), I. Attwell and R. Karadottir)
• 2007-2011: MRC Capacity building PhD studentship 鈥淏iology of neural stem cells in the adult mouse forebrain: a transgenic approach鈥�
• 2006-2009: MRC New Investigator award 鈥淕eneration of neuronal diversity in the developing telencephalon鈥�
• 2002-2007: MRC Programme grant, 鈥淣eural stem cells and neuroglial lineages in the central nervous system鈥� (with W. Richardson (PI) and H.K. Smith)

Huliang Li

• 2022-2024: BBSRC Research Grant, Co-I, Metabolic and behavioural phenotyping platform for obesity, diabetes, aging and exercise studies in mouse (BB/W020009/1 with Prof. Stefan Trapp and others)
• 2021-2023: Royal Society Cost Share Grant, PI, Collaborative Study of the Effects of Natural Molecules on Reactive Astrocytes (IEC\NSFC\201134)
• 2019-2023: BBSRC Research Grant, Co-PI, Control of oligodendrocyte development by Olig2 and chromatin remodelling complexes (with Prof. Bill Richardson, BB/S008934/1)
• 2019-2022: Newton International Fellowship Grant, UK-PI, Towards CRISPR/Cas9-mediated gene correction for inherited retinal disease (NIF\R1\181649 with Dr Jing An)
• 2018-2022: BBSRC Research Grant, PI, Cholesterol esters of oligodendrocytes in developmental and ageing brain (BB/S000844/1)
• 2018-2020: Newton International Fellowship Grant, UK-PI, Improving the therapeutic potential of adult stem cells for Alzheimer's disease treatment (NIF003\1003 with Dr Yajun Wang)
• 2017-2019: Alzheimer's Research UK Pilot Grant, PI, Cholesterol esters in oligodendrocytes and the implications for Alzheimer鈥檚 disease (ARUK-PPG2017B-013)
• 2016: British Council Researcher Links Grant, PI, Collaborative strategies to study myelin and fight against multiple sclerosis and other white matter diseases. (227225126)
• 2015-2018: Newton Advanced Fellowship Grant, UK-PI, Towards rapid and efficient production of oligodendrocyte precursors from human pluripotent stem cells (with Dr Wenlin Li)
• 2014-2017: BBSRC Research Grant, PI, Transgenic approaches to understanding astrocyte heterogeneity (BB/L003236/1)

Matthew Swire

• 2023-2028: MRC Career Development Award, How does Adaptive Myelination Re-shape Neural Circuits During Learning? (MR/X019977/1)

Related programmes

Our members contribute to BSc and master's degrees within the Faculties of Medical Sciences听and Life Sciences. We also have a long and excellent track record in providing high-quality training to undergraduate, master's and PhD students interested in the areas of neuro glia development, plasticity and disease. More than 30 PhD students have trained with us, graduated and moved on to further research positions in academia, industry and UK government positions.

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