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Brenda Williams

Dr

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Research interests

Brief Biography

Brenda gained a PhD in neurobiology from University College London in 1984 and honed her research skills through post-doctoral positions at Cancer Research UK, the National Institute for Medical Research and the Dana Faber Cancer Institute. In 1996 she became a principal investigator and lecturer at University College London before moving to the Institute of Psychiatry, Psychology and Neuroscience in 2000, where she is a Senior Lecturer in the Department of Basic and Clinical Neuroscience.

The research within Brenda’s laboratory focused on understanding the molecular and cellular processes that control the fate of neural stem cells (NSCs), not only as a means for understanding neurodevelopment but also to harness the full therapeutic potential of these cells for the treatment of disease. More recently, her research has explored how glial cells and glial-neuronal interactions in the diseased brain may influence disease progression.

In parallel with her research career, Brenda teaches on the campus based undergraduate and postgraduate neuroscience taught programmes and works tirelessly to enhance the student experience through developing initiatives to help transition form undergraduate to postgraduate study, expanding skills training opportunities to enhance employability, and evaluating and improving assessment and feedback practices. She firmly believes in widening participation and coordinates annual work experience courses for school children from across London and visits schools to encourage pupils to consider careers in the sciences. She received a supervisory excellence award from King’s College London in 2010 and became a fellow of the Higher Education Academy in 2014.

In September 2015 Brenda took up an education focused position at KCL as the Lead for the MSc in the Psychology and Neuroscience of Mental Health by distance learning; overseeing the design and development of this exciting and innovative course.

 

Research Overview

Much of the research within the laboratory the Williams' laboratory focused on understanding how cellular diversity is generated in the developing central nervous system. Understanding the molecular and cellular processes that control the differentiation of neural stem cells (NSCs) and the neural progenitor cells (NPCs) they generate is essential not only to our understanding of neurodevelopment but also in enabling us to harness the full potential of these cells for the treatment of neurodegenerative disease. More recently, our research has expanded to explore the role of endogenous neurogenesis in the diseased brain and to understanding how glial cells and glial-neuronal interactions in the diseased brain may influence disease progression. We have also begun to use NPC lines and induced pluripotent stem cells (iPSCs) as tools to develop platforms for drug discovery.

 

Using cell culture to address fundamental questions in neurobiology

The majority of our studies are carried out using primary neural cell cultures. These cultures provide a simple, well-defined system that can be easily controlled and manipulated. We generate not only mixed neuronal/glial cultures but also pure cultures of neurons and the different glial cell types (astroctyes, microglial cells, oligodendrocytes). Using such cultures we can ask direct questions on how the environment influences cell division, differentiation and survival by exposing cultures to different compounds or by the co-culture of different cells types. In addition, we can engineer specific cell types to express, or fail to express, specific genes and determine the impact of this change on their own fate or that of neighbouring cells. We also carry out similar experiments using human neural stem cell lines that can be differentiated into different neural cell-types when grown under specific cultures conditions.

 

Specific Research interests and Collaborations

To understand how glial cells (astrocytes and microglia) contribute to neurodegeneration,

Collaborator: Dr. Jonathan Cooper, KCL, Institute of Psychiatry.

Using pure populations of each glial cell type isolated from either wild type mice or mouse models of the disease, we are investigating the impact of ‘diseased’ astrocytes or microglia on neuronal survival and the impact of astrocyte/microglial interactions on neuronal survival in situation where only astrocytes, only microglia or both glial cell types are isolated from the diseased brain. This will allow us to evaluate the contribution of specific cell-cell interactions to the disease process. Most recently, we have been applying this strategy to juvenile Batten disease (JNCL), the most common of a group of fatal inherited neurodegenerative disorders caused by a mutation in the Cln3 gene, and for which no effective treatments are available.  

 

Cell based systems for drug discovery in JNCL

Collaborator: Dr. Jonathan Cooper, KCL, Institute of Psychiatry.

Attempts to design effective therapies for JNCL are hampered by a poor understanding of the consequences of Cln3 mutation. We have adopted the fundamental approach of asking how each cell type in the brain is affected in JNCL mice (see above), and have defined defects in both astrocytes and microglia and shown that these mutated glial-cell negatively impact neuronal health. JNCL neurons are themselves also compromised rendering them more vulnerable to the influence of Cln3 deficient glia. We are now determining whether the same phenotypes are evident in human neurons and glia, and how robust these phenotypes are for drug screening.

 

The axon initial segment in disease

Collaborators: Dr. Jonathan Cooper, KCL, Institute of psychiatry, Matthew Grubb, KCL, MRC Centre for Developmental Neurobiology.

The axon initial segment (AIS) is an important structure within healthy neurons that determines those proteins that reach the axon and modulates neuronal excitability and the initiation of axon potentials. However, the position of the AIS is not fixed and moves distally along the axon when wild type cultures are chronically depolarised with high levels of potassium. This is thought to represent a compensatory response to chronic depolarisation, altering the probability of neuron firing. Since these properties have relevance in disease, we are investigating AIS biology in mouse models of Batten disease, and in particular the impact that diseased and healthy glial have on AIS position.

 

Manipulating the expression of susceptibility genes for schizophrenia and aggression in human neural stem cell lines.

Collaborators: Dr Nick Bray and Professor Jack Price, KCL, Institute of Psychiatry.

We are beginning to manipulate the expression of established susceptibility genes for schizophrenia (starting with DISC1) and aggression (starting with Nos1) in human neural cell populations in order to understand their function and ultimately help identify downstream targets for therapeutic intervention.

Research interests (short)

Neural stem/progenitor cell biology, neuron-glial interactions, Neuronal ceroid lipofuscinosis (Batten disease), in vitro platforms for drug screening.

Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

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