The regulation of protein synthesis and turnover in the adaptive immune system

• Funding – self-funded/externally sponsored applicants   (PhD Fees can be found here)
• Applications are accepted year round
• Standard Entry dates – January and September
• Applicants are expected to have a degree (equivalent of Honours or Masters) in a relevant discipline.

This project aims to understand how B lymphocytes, key cells of the adaptive immune system, regulate protein synthesis and turnover. B lymphocytes (B cells) produce antibodies which bind to pathogens such as viruses and bacteria and target them for destruction. Short-lived and long-lived antibody producing B cells provide rapid and durable protection against infection and B cells play a vital role in providing an effective vaccine response. B cell dysfunction is linked to a range of diseases and there is intense interest in understanding the core activities of B cells and how these are impacted in disease settings and in response to ageing. B cells are protein production factories, with each cell capable of producing up to 10,000 antibodies every second. This is equivalent to the cell producing its own mass in antibodies every day. Given the scale of antibody production, protein synthesis and turnover (proteostasis) must be tightly regulated to maintain health. 

In this project we want to understand how B cells maintain proteostasis during their activation and differentiation into antibody producing effector populations. Critical knowledge gaps exist in our understanding of the proteostasis machinery used by B cells and how this is impacted under conditions of cellular stress including nutrient stress. Using high-sensitivity quantitative proteomics we will map the core machinery for protein degradation, including components of the ubiquitin-proteasome system, and elucidate the impact of modulating this machinery on cell phenotypes. This project will provide novel mechanistic insights into how B cells regulate protein turnover, which is valuable for translating into ageing and disease settings in the future and may lead to novel strategies for modulating B cell activities. This project will also provide the ideal opportunity for a PhD student to master a range of molecular and cell biology skills at the forefront of the field including biochemistry, quantitative proteomics, big data, targeted gene editing and immune phenotyping.