Website warwickuni University of Warwick
Closing date: 23rd November
A funded PhD at the University of Warwick to uncover the molecular functions of TMEM131, a protein essential to vertebrate development and implicated in Down syndrome and Alzheimer’s disease, through the Midlands Integrative Biosciences Training Partnership. Supervised by Dr John James and Dr Michael Smutny. Open to students worldwide. See more funded PhDs.
Dr John James, Dr Michael Smutny
Funded PhD Project (Students Worldwide)
About the Project
The development of vertebrate animals from a single fertilised cell to the fully formed adult is an astonishingly well-choreographed sequence of events, which is made more remarkable by being so faithfully recapitulated on each attempt. Previous work from our lab identified a gene product that was important in the process of immune cell development. Subsequent experiments have shown that this protein, named TMEM131, is in fact essential for viable offspring of vertebrates more generally, where TMEM131 loss causes embryonic lethality in mice and zebrafish.
There is very little data available for the function of TMEM131 in cells, with the postulated function from the limited published literature incompatible with its developmental role. The only available evidence for ascribing a compatible function to TMEM131 comes from genetic association studies, where it has been found to be upregulated during thymic development, to have dysregulated methylation in patients with chromosome-21 trisomy (Down’s Syndrome) and its upregulation has been implicated in the development of neurological disorders such as dementia and Alzheimer’s disease. Pertinently, the TMEM131 gene is present and extremely well conserved throughout the vertebrate lineage. For example, the zebrafish homologue shares 72% identity, 84% similarity at the protein level.
The central goal of this project is to uncover the molecular functions of TMEM131 in development and cell function, with the hypothesis that it is a chaperone that helps other developmentally important protein complexes to form correctly. We will characterise the molecular details of TMEM131 in a reconstituted cellular system and in the zebrafish model organism where embryo development can be directly observed. The opportunities for extending the research in myriad different directions based on the identified function, provide a very exciting new research project for a PhD student.
To apply for this job please visit www.findaphd.com.
