MSc by Research Programme: ADP-ribosylation in the aging nervous system

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

ADP-ribosylation is a fundamental posttranslational modification where ADP-ribose is linked on to target proteins by ADP-ribose transferases and removed by the ADP-ribose hydrolases. Emerging data implicate ADP-ribosylation in maintaining the health of the nervous system; mutations in the genes that encode the enzymes that reverse ADP-ribosylation cause neurodegenerative disease in humans and pharmacological inhibition of the ADP-ribose transferases is therapeutically beneficial in various cellular and animal models of human neurodegenerative diseases such as stroke, Parkinson’s disease and motor neuron disease (reviewed in 1). This suggests that ADP-ribosylation regulates key proteins involved in brain aging, however what these proteins are and how they are regulated by ADP-ribosylation is unknown. To elucidate the proteins and underlying mechanisms that regulate brain aging, the student will use an interdisciplinary approach that combines genetics of the fruit fly with molecular and cellular approaches to determine the role of nuclear ADP-ribosylation in the aging and diseased nervous system of the fly (AIM1) and in human iPSC-derived neurons (AIM2). At the end of this project the student will have identified novel aspects of ADP-ribosylation in the normal and diseased nervous system.

Background reading 1-5

[1] McGurk, L., Rifai, O. M., and Bonini, N. M. (2019) Poly(ADP-Ribosylation) in Age-Related Neurological Disease, Trends Genet 35, 601-613.
[2] McGurk, L., Mojsilovic-Petrovic, J., Van Deerlin, V. M., Shorter, J., Kalb, R. G., Lee, V. M., Trojanowski, J. Q., Lee, E. B., and Bonini, N. M. (2018) Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis, Acta neuropathologica communications 6, 84-95.
[3] McGurk, L., Gomes, E., Guo, L., Mojsilovic-Petrovic, J., Tran, V., Kalb, R. G., Shorter, J., and Bonini, N. M. (2018) Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting Liquid Demixing and Stress Granule Localization, Molecular cell 71, 703-717 e709.
[4] McGurk, L., Gomes, E., Guo, L., Shorter, J., and Bonini, N. (2018) Poly(ADP-ribose) engages the TDP-43 nuclear-localization sequence to regulate granulo-filamentous aggregation, Biochemistry 57, 6923-6926
[5] McGurk, L., Berson, A., and Bonini, N. M. (2015) Drosophila as an In Vivo Model for Human Neurodegenerative Disease, Genetics 201, 377-402.