3.5 Year MRC PhD Programme: New biomarkers for Parkinson’s disease based on dissection of LRRK2 kinase biology

Parkinson’s disease is a progressive neurological condition for which there are currently no cures, that affects over 10 million people worldwide. Until recently the causes of Parkinson’s disease were unknown, but breakthrough in genetic analysis of Parkinson’s patients have revealed inherited mutations in at least 22 genes that cause or are major risk factors for Parkinson’s [Ref 1]. Little is understood about the regulation and function of the majority of the proteins encoded by Parkinson’s genes. The LRRK2 protein kinase is one of the most commonly mutated genes that causes familial inherited Parkinson’s. As the disease-causing mutations activate LRRK2 there is great interest to develop inhibitors that target LRRK2 as a potential novel therapy to treat Parkinson’s. Many Pharmaceutical companies have elaborated highly selective and potent LRRK2 inhibitors and the hope is that these may enter clinical trials in the next 18 months. The recent work that our laboratory has undertaken has excitingly established that LRRK2 phosphorylates a group of 14 Rab GTPases in the middle of their effector binding domain [Refs 2 & 3].

The PhD project will be to discover whether mutations in other Parkinson’s genes also stimulate LRRK2 activity and induce phosphorylation of Rab proteins. You would elucidate underlying mechanisms of such interactions. You would also collaborate with clinicians and pharmaceutical companies to define whether hyper-activation of LRRK2 and Rab protein phosphorylation can be used as a biomarker for Parkinson’s disease. This is important as it would provide a test for which patients might benefit from LRRK2 inhibitor drugs. In this project, you will gain experience in the state of the art methodologies for studying signalling pathways and Parkinson’s biology. This would include protein biochemistry, CRISPR/CAS9 genome editing, mass spectrometry, kinase and Rab GTPase biology, molecular biology, tissue culture and handling of clinical samples.

The University of Dundee is delighted to be recruiting for five PhD studentships, funded for 3.5 years, to start in September 2017. These projects bring together leading experts from the School of Life Sciences (SLS), the School of Medicine (SoM) and the School of Science and Engineering (SSE) to train the next generation of scientists at the forefront of international science. The outstanding biomedical research at the University of Dundee was recognised by its high rankings in REF 2014, with Dundee rated as the top University for Biological Sciences in the UK.

Eligibility: Applications for these MRC studentships are invited from excellent UK* students expected to hold (or be about to achieve) at least a 2:1 Honours degree in a relevant subject.

*Some EU students may be eligible for a full award if you meet Research Council residency criteria and other exceptions may apply.