About the Project
Neurons in the brain are highly metabolically active and produce damaging reactive oxygen species (ROS) when at rest and when highly active. The build-up of cellular damage by neuronal ROS is thought to contribute to cognitive decline with age. However, ROS are not just deleterious, they provide an important signal for synapse function in a range of important processes, such as memory formation. How do neurons distinguish and respond appropriately to beneficial or toxic levels of ROS? We have recently found that low and high levels of ROS differentially activate two alternative kinase signalling pathways that subsequently alter the protein subunit composition of the transcription factor AP-1. We hypothesise that this occurs through differential phosphorylation of the AP-1 subunits. Using the fruit fly (Drosophila), which has fewer potential AP-1 subunit genes and phosphorylation sites, the student will determine the kinase signalling that drives AP-1 composition under low and high levels of ROS. We have also developed a co-expression system allowing production of soluble recombinant AP-1 heterodimers (this is a first) for in vitro validation of our in vivo findings. Finally we will use genomic analyses to ascertain how differential AP-1 phosphorylation and composition alters the transcriptional targets of AP-1 in neurons.
The White Rose DTP in Mechanistic Biology is committed to recruiting extraordinary future scientists regardless of age, ethnicity, gender, gender identity, disability, sexual orientation or career pathway to date. We understand that commitment and excellence can be shown in many ways and have built our recruitment process to reflect this. We welcome applicants from all backgrounds, particularly those underrepresented in science, who have curiosity, creativity and a drive to learn new skills.
This project is part of the BBSRC WR DTP in Mechanistic Biology. Appointed candidates will be fully-funded for 4 years. The funding includes:
Tax-free annual UKRI stipend (£15,285 for 2020/21)
UK tuition fees (£4,473 for 2021/22)
Research support and training charges (RSTC)
We aim to support the most outstanding applicants from outside the UK and are able to offer a limited number of bursaries that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.
ENTRY REQUIREMENTS: Students with, or expecting to gain, at least an upper second class honours degree, or equivalent, are invited to apply. The interdisciplinary nature of this programme means that we welcome applications from students with backgrounds in any biological, chemical, and/or physical science, or students with mathematical backgrounds who are interested in using their skills in addressing biological questions. If English is not your first language, you will need to meet the minimum entry requirements for your country. Please check our website: https://www.york.ac.uk/study/postgraduate-research/apply/international/english/
START DATE: 1st October 2021