PhD Studentship: Effect of Alzheimer’s Disease Risk Variants on Microglial Cell State Transitions in Response to Pathology. MRC GW4 BioMed DTP PhD Studentship 2024/25 Entry, PhD in Clinical and Biomedical Sciences

Project title: 

Effect of Alzheimer’s disease risk variants on microglial cell state transitions in response to pathology. MRC GW4 BioMed DTP PhD studentship 2024/25 Entry, PhD in Clinical and Biomedical Sciences

The GW4 BioMed2 MRC DTP is offering up to 22 funded studentships across a range of biomedical disciplines, with a start date of October 2024.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

About the GW4 BioMed2 Doctoral Training Partnership

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 38 students over 2 cohorts in its second phase.

The 80 projects available for application, are aligned to the following themes;

• Infection, Immunity, Antimicrobial Resistance and Repair
• Neuroscience and Mental Health
• Population Health Sciences

Applications open on 4nd September 2023 and close at 5.00pm on 1st November 2023.

Studentships will be 4 years full time. Part time study is also available.

Project Information

Research Theme: Neuroscience & Mental Health

Summary:

Microglia are strongly linked to Alzheimer’s disease (AD), supported by significant cell-type specific genetic association. However, there is a substantial gap in our understanding of how genetic variation affect microglial response to pathology. This project will use culture models to uncover the mechanisms associated with microglial activation states using a multidisciplinary approach including microscopy, electrophysiology, epigenetics, and bioinformatics

Description:

A significant proportion (~25%) of Alzheimer’s disease (AD) risk loci map to genes preferentially expressed in microglia and associate with pathways key in regulating microglial activation and cellular state. It is also well established that the epigenome plays a pivotal role in the regulation of microglial activation states. We previously identified deficits in microglial response to inflammatory modulators and effects on activation states if cells harboured TREM2 mutations associated with AD, providing an excellent model of sub-optimal microglial activation.

The project will use human iPSC-derived microglia and neurons to study:

“How AD risk variants alter the ability of microglia to respond to pathological insults” Objectives and learning outcomes for the student:

1. Develop expertise in iPSC culturing to generate complex models to assess microglial response to pathology
2. Develop skills in electrophysiology and super-resolution imaging to assess differences in microglial physiology and cellular states when harbouring genetic variants
3. Develop bioinformatic skills to identify new regulatory pathways that are altered in disease variant microglia, affecting cell state transitions

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