This is a 7 week project which will run from 12th June to 28th July 2023.
The stipend available is £180 per week. Please apply by submitting your CV and a covering letter to email@example.com by noon on Friday 3rd February 2023. This scheme is only open to University of Leeds Science Students and Medical Students who are between the end of their second year and the end of their penultimate year (but not intercalating students). Please note that students currently in their first or final year are NOT eligible to apply.
Therapeutic potential of HDAC inhibitors for multiple sclerosis.
Professor Ian Wood
Recently, inhibitors of histone deacetylase enzymes (HDACs) have been identified as having potential therapeutic value for a range of neuronal disorders including multiple sclerosis and other neurodegenerative diseases . The HDAC inhibitors have been shown to have neuroprotective and anti-inflammatory properties yet their mechanism of action remains unidentified. We have recently shown that microglia activation by a number of insults (eg LPS, interferon and Amyloid beta) can be reduced by HDAC inhibitors . Using siRNA we have identified HDAC1 and HDAC2 as the important HDAC enzymes for this response . Whilst still don’t know the mechanism by which HDAC inhibitors block microglia activation we have shown that it doesn’t require new protein synthesis so is unlikely to be a result of the well characterised effect of these inhibitors on increasing gene expression. We are currently investigating the cellular mechanism(s) involved in the inhibition and identifying the molecular targets we think are involved such as NF-Kb, PTEN and STAT1. We use a lot of molecular and biochemical techniques to uncover the important mechanisms at play and the project would suite a student with an interest in biochemistry or the molecular aspects of biomedical sciences or biology. Work in this project is likely to involve; the use of cell culture methods, expression and visualisation of GFP fusion proteins, functional assays to quantify cell responses such as proliferation as well as molecular approaches to quantify cytokine production and changes in gene and protein expression.
1.Durham, B.S., R. Grigg, and I.C. Wood, Inhibition of histone deacetylase 1 or 2 reduces induced cytokine expression in microglia through a protein synthesis independent mechanism. J Neurochem, 2017. Oct;143(2):214-224