Course: Doctor of Philosophy
Supervisor: Dr. Ioannis P. Nezis
I am a PhD student interested in deciphering the interplay of the key components of macroautophagy. Ranging from development, to ageing, to the immune response, autophagy is thought to mediate a wide range of homeostatic processes, both at the cellular and organism levels. I aspire to build a career in academia after I finish this course.
Drosophila melanogaster is a very useful organism for genetic studies, due to low gene redundancy, low number of functional paralogues compared to mammals and ease of manipulating its genetic makeup. With a generation cycle of 11 days* and lifespan of about 60 days*, it is easy to observe phenotypes over the lifespan of the organism, which is especially useful for investigations into late-onset diseases.
Autophagy is a selective process of sequestering deleterious cellular material into double-membrane compartments, called autophagosomes, followed by their fusion with lysosomes and the subsequent hydrolysis of the autophagic cargo. The specificity of this process is mediated by cargo-identifying selective autophagy receptors, of which there are at least 6 in mammals (p62/SQSTM1, NBR1, NDP52, Nix, optineurin and Stbd1), but only 1# in Drosophila, Ref(2)p, homologue of mammalian p62. These receptors bind to Atg8/LC3 family proteins, which are found on both sides of the autophagosome membrane. A key focus area is on finding and characterising novel autophagy receptors in Drosophila and their regulatory roles, within the autophagy framework.
In my project I am using biochemical methods to investigate a number of candidate selective-autophagy receptors. The interconnected nature of autophagy-mediated processes sees me looking at aspects of fly ageing, changes in its inate immune response, and the endocrine relationship between its brain, fat body and digestive system.
* - at optimal conditions (24˚C and 70% RH)
# - a second potential candidate (bluecheese, homologue of mammalian Alfy) has been suggested
Publications and appearances
Review: Nitha C. Mulakkal, Peter Nagy, Szabolcs Takats, Radu Tusco, Gábor Juhász, and Ioannis P. Nezis, “Autophagy in Drosophila: From Historical Studies to Current Knowledge,” BioMed Research International, vol. 2014, Article ID 273473, 24 pages, 2014. doi:10.1155/2014/273473
Conference: 1st UK autophagy network meeting at Warwick University - presented work in a talk
Conference: 2nd UK autophagy network meeting at Edinburgh University - presented a poster
See autophagy.uk for details.