PhD in Medicine: Characterising the pathways to abnormal protein aggregation in dementia in Drosophila and induced pluripotent stem cell models

Outline

We have evidence in HD that specific amino acid changes in genes of the autophagy pathway lead to early onset of disease. We wish to examine the effects of knocking out the genes containing these changes and to directly model these specific changes in the orthologous proteins in HD mutant Drosophila models. If the changes lead to altered dynamics or clearance of mutant huntingtin we will characterise the kinetics of this effect in flies using assays of autophagy. These include the signalling pathways triggering activation of autophagy, the machinery governing formation of autophagic vacuoles and the processes leading to their clearance by lysosomes.

We will go on to characterise the relevant pathway using the same variants in fly models of AD and PD to investigate whether this constitutes a common pathway for clearance of mutant aggregated proteins.  These results will then be validated in induced pluripotent stem cell models.

What is funded

Full UK/EU tuition fees

Duration

3 years

Eligibility

You will hold or expect to achieve a First or Upper Second Class degree in a relevant area (e.g. neuroscience, psychology, anatomy, physiology, natural sciences). As this is a training doctorate, previous research experience is not essential.