Protein O-GlcNAcylation is a post-translational modification that is emerging as being neuroprotective by “shielding” proteins involved in neurodegenerative proteinopathies (e.g. ). The van Aalten lab is studying the biological and molecular mechanisms underpinning this modification using a combination of biochemistry, structural biology and mouse/Drosophila genetics [2,3,4]. Neurodegenerative diseases are increasingly recognised as not necessarily neuronal cell autonomous .
Mutations in the NEK1 kinase have recently been identified in patients with familial motor neurone disease (MND). NEK1 encodes a kinase of 1258 amino acids and previous studies have linked NEK1 activity to regulation of DNA repair pathways. How defects in DNA repair lead to MND is currently unknown. The project involves cutting-edge technologies carried out in a world-class institution to characterize the function of NEK1 in relevant neuronal systems. The project will also determine how mutations lead to MND, and analyse the impact of these mutations on cell responses to DNA damage.