Research Fellows Directory
Dr Helena Cimarosti
University of Bristol
Alzheimer’s disease (AD) is the most common cause of chronic dementia among the elderly, with an estimated 40 million patients diagnosed with this condition worldwide. Even more crucially, prognoses predict this number to almost double every 20 years. Therefore, the mechanisms underlying neuronal death in AD are the focus of intense research interest.
SUMOylation is a process in which ‘SUMO’ proteins are attached to other target proteins altering their activity, stability and/or localization, in various cellular compartments. It has emerged recently that SUMOylation is involved in multiple neuronal signalling cascades and is strongly implicated in many neurodegenerative diseases, including AD.
The purpose of this fellowship is to define the roles of SUMOylation in the development of AD. Our hypothesis is that stress-induced degradation of SENP3, a deSUMOylation enzyme, increases SUMOylation of a protein known as Drp1. This is directly relevant to AD because SUMOylated Drp1 prevents the cell death. Thus, we propose that decreasing SENP3 levels and/or enhancing Drp1 SUMOylation may be beneficial in AD.
To investigate this we will use molecular biological techniques to manipulate levels of SUMOylation and deSUMOylation pathways in cell culture and transgenic models of AD. These experiments will provide greater understanding of basic molecular and cellular processes involved in neuronal death and survival, and will reveal if SUMOylation represents a potentially tractable target for therapeutic intervention. In the longer term, it may identify specific protein targets and/or protein interactions amenable for drug development to reduce brain damage suffered by AD patients.
Interests and expertise (Subject groups)