Molecular mechanisms of selective autophagy during the course of ageing

Lead Research Organisation: University of Warwick
Department Name: School of Life Sciences

Abstract

Advances in modern medicine have led to a significant increase in human life expectancy. A consequence of this has been the increase of the frequency of ageing-related diseases. Recent studies have indicated that a breakdown of the proteolytic cellular machinery of autophagy in cells, is involved in the development of ageing-related diseases. Autophagy is an essential catabolic process that involves the degradation of cytoplasmic material through the lysosomal pathway. Cells use autophagy to generate materials and energy when conditions become unfavourable. They also use this process to clear damaged cellular components. We will use the fruit fly Drosophila melanogaster as a genetically modifiable model organism to investigate the mechanisms of selective autophagy during ageing in vivo. These mechanisms are very similar between fruit flies and humans, so the results will have direct relevance to human health.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M01116X/1 01/10/2015 30/09/2023
1897957 Studentship BB/M01116X/1 02/10/2017 30/09/2021 Laura Prisco
 
Description The aim of the work is to identify the role of UbcD4 in autophagy.

Investigating the role of UbcD4 in immunity - The results show unconvincing evidence that the absence of UbcD4 causes changes in AMP expression. Tusco et al., 2017 have shown that immunity and autophagy are linked and a recent paper by Park et al., 2016 has demonstrated UbcD4's implication in immunity. Previous results in the lab showed a slight induction (8-fold increase) of dpt in UbcD4 CRISPR flies, compared to w1118 type flies.

Investigating the interaction between Atg8a and UbcD4 - There is clear evidence of an interaction between UbcD4 and Atg8a. The UBA domain of UbcD4 is unlikely to be the region responsible for this interaction due to there being an observable interaction between UbcD4-?UBA and Atg8a. Mass spectrometric analysis on immunoprecipitated samples is currently underway to investigate this interaction further.

The role of UbcD4 in autophagy - UbcD4 CRISPR mutants show increased Ref(2)P and FK2 expression in both 1 week old and 4 week old flies when compared to wild-type flies. FK2 aggregates also appear larger in Atg8a;UbcD4 double mutant females compared to UbcD4 CRISPR mutants and wild-type flies.
Exploitation Route Autophagy is a prime target for pharmaceutical applications. Further elucidating the process and the functions of involved proteins could help identify drug targets for pathologies in which autophagy is implicated.
Sectors Pharmaceuticals and Medical Biotechnology