PhD Studentship: Investigating the interaction of APOE4 with TDP43 proteinopathy in driving neurodegeneration

PhD Studentship:

Investigating the interplay of APOE4 with TDP43 proteinopathy in driving neurodegeneration

Mission Description

The College of Exeter’s Dwelling Programs Institute is inviting functions for a PhD studentship fully-funded by BRACE to begin on twenty fifth September 2023 or as quickly as doable thereafter. 

TDP43 or (TARDBP) is an RNA-binding protein with crucial features in neurons, together with different splicing and microRNA biogenesis. In lots of neurodegenerative ailments related to dementia comparable to Frontotemporal dementia (FTD), limbic related TDP43 encephalopathy (LATE) and Alzheimer’s illness (AD), TDP43 mislocalizes to the cytoplasm and often aggregates into inclusions that may result in neurodegeneration. Nevertheless, the downstream results of TDP43 mislocalization on neurons are incompletely understood. Genetic variants in sure genes are related to elevated threat of neurodegenerative illness. For instance, the APOE4 allele is related to elevated threat of late-onset AD and LATE. Nevertheless, whether or not these genetic variants act synergistically or independently of TDP43 mislocalization is essentially unknown. On this venture, the scholar will examine the impact of the APOE4 allele on human iPSC-derived neurons within the presence or absence of TDP43 pathology and deploy a mixture of imaging-based mobile assays and genomic instruments to know the mechanisms driving neuronal dysfunction.

The proposed examine is not going to solely develop a completely characterised new mannequin to review TDP43 proteinopathies however can even spotlight how genetic threat synergizes with a key biochemical hallmark to drive neuronal dysfunction in dementia. Moreover, the genomic research highlighted will uncover new candidates for therapeutic intervention.

The coed will likely be primarily based within the LSI, an interdisciplinary initiative between Engineering, Arithmetic, Physics, Biosciences and the Medical College. The LSI homes a high-content high-throughput imaging platform that may conduct phenotypic screens on neurons. We even have entry to an imaging suite that features confocal and super-resolution microscopes, and plate readers for mixed fluorescence/luciferase assays for neuronal viability read-outs enabling the scholar to obtain coaching in state-of-the-art gear for phenotypic assays. They are going to be part of a rising LSI early profession researcher community (ECRN) comprised of over 100 PhD college students and post-doctoral fellows. The coed can even be embedded inside the Complicated Illness Epigenetics Group on the Medical College. They may be part of a dynamic group with a vibrant setting for early profession researchers on the Wellcome Wolfson Centre for Medical Analysis primarily based within the new RILD constructing outfitted with leading edge amenities for genomics analysis. The coed will obtain coaching in stem-cell biology, state-of-the-art imaging for phenotypic assays in addition to genomics and bioinformatics. They may work together with researchers throughout arithmetic, physics and computational neurobiology gaining a large expertise in several however related disciplines that may assist body future postdoctoral grants and fellowships.

This award offers annual funding to cowl Dwelling tuition charges and a tax-free stipend.

For college kids who pay Dwelling tuition charges the award will cowl the tutoring charges in full, plus a minimum of £18,622 per yr tax-free stipend. 

Entry necessities

Candidates for this studentship should have obtained, or be about to acquire, a First or Higher Second Class UK Honours diploma, or the equal {qualifications} gained outdoors the UK, in an acceptable space of science or know-how. 

If English isn’t your first language you’ll need to fulfill the required stage as per our steering at https://www.exeter.ac.uk/pg-research/apply/english/

The deadline for functions is midnight on Sunday fifteenth October 2023.