University College London Featured PhD Programmes
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MSc by Research Programme: LRRK2 kinase pathway activation during infection

  • Full or part time
  • Application Deadline
    Thursday, July 16, 2020
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

This course allows you to work alongside our world renowned experts from the School of Life Sciences and gain a ’real research’ experience. You will have the opportunity to select a research project from a variety of thematic areas of research.

You will be part of our collaborative working environment and have access to outstanding shared facilities such as microscopy and proteomics. Throughout your year, you will develop an advanced level of knowledge on your topic of interest as well as the ability to perform independent research in the topic area. Alongside basic science training in experimental design, data handling and research ethics, we will help you to develop skills in critical assessment and communication. This will be supported by workshops in scientific writing, presentation skills, ethics, laboratory safety, statistics, public engagement and optional applied bioinformatics.

The period of study is one year full-time or two years part-time research, which includes two months to write up the thesis. Please apply via the UCAS postgraduate application form: https://digital.ucas.com/courses/details?coursePrimaryId=c735d826-42b6-ca1f-50db-2a3ac6f68718

LRRK2 functions as a kinase and hyperactivating mutations cause 1-2% of all cases of Parkinson’s disease. LRRK2 is highly expressed in immune cells and LRRK2 signalling appears to play a role in immune defence mechanisms. In fact, increased LRRK2 activity may protect against opportunistic infections, but later in life, increase the risk of developing Parkinson’s disease, a concept known as antagonistic pleiotropy. This project plans to explore LRRK2 kinase pathway activation throughout the course of an infect exacerbation in patients with chronic lung disease. For this, neutrophils from peripheral blood and sputum will be isolated at up to 3 timepoints: at the time of presentation with an acute infect exacerbation (1), at the end of a course a course of antibiotics / infect resolution (2) as well as once in between (3). Neutrophils will be processed and analysed by multiplex quantitative Western blotting for LRRK2 controlled phosphorylation of its endogenous substrate Rab10 which is a proxi for LRRK2 kinase activation status (Biochem J. 2018 Jan 2;475(1):23-44. doi: 10.1042/BCJ20170803.). This is an exciting translational research opportunity. The student would work with leading clinicians and research nurses at the Ninewells site - who will facilitate recruitment of patients and bio-sample collection – while being mainly based at the MRC Protein Phosphorylation and Ubiquitylation Unit.

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