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.
Organisations
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M01116X/1 | 01/10/2015 | 31/03/2024 | |||
| 1897957 | Studentship | BB/M01116X/1 | 02/10/2017 | 04/10/2022 | 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 |
| Description | Brilliant Club Scholar's Programme |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | I have been involved with the Brilliant Club's Scholars Programme. The aim of the role is to design courses based on my own scientific research and subsequently teach the course in a set number of lessons, giving students individual feedback on the work they produce and their engagement. So far I have undertaken Brilliant Club training, designed a course outline and have begun creating the final course document. The Brilliant Club's work is particularly important now as many students, particularly from lower income backgrounds, risk falling further behind than their peers from higher income families. Making PhD level science accessible for younger audiences is also of significance and has the potential to positively impact students' attitudes towards STEM subjects by reinforcing the knowledge they already have and promoting their critical thinking skills. |
| Year(s) Of Engagement Activity | 2020,2021 |
| URL | https://thebrilliantclub.org/the-scholars-programme/ |