Investigating the (Patho) Physiological Importance of S-Acylation

Intellectual disability is a condition affecting up to 1% of the general population and involves a defect in intellectual and adaptive skills. This condition can be caused by gene mutations, environmental factors or injury, and there are no available drug treatments or cures. Neurodegeneration typically occurs in later life and involves the loss of function and death of neurons in the brain (common neurodegenerative disorders include Alzheimer’s disease, Huntington's disease and Parkinson’s disease). There is also no cure for these conditions. The aim of this project is to understand the function of specific proteins in the brain and nervous system and their links with disease. The proteins of interest attach fats to other proteins and have been implicated in disorders including intellectual disability and neurodegeneration.

It is important to undertake this work because the proteins being investigated have been linked to neurological disorders, including intellectual disability and neurodegeneration. Intellectual disability is characterized by below-average intelligence or mental ability and a lack of skills necessary for day-to- day living, whereas neurodegeneration refers to the progressive loss of function and death of neuronal cells in the brain. By studying the functions of these proteins we hope to generate new insight into the changes that occur in the nervous system in these and other neurological conditions, which will lead to the identification of potential new treatments.

The main outputs at the end of this project are expected to be new insights into molecular and cellular changes that occur in the brain in intellectual disability and other neurological disorders. This may include the identification of novel biomarkers of disease or new drug targets.

The main beneficiaries of the outputs generated in the period of this licence will be other scientists investigating the function of related proteins. The data we report will provide new ideas and insight to advance their studies. In addition, the research will also benefit clinical researchers who are investigating the underlying causes of intellectual disability and related disorders- our research will also provide important new insights that may advance the work of others in this general area. Our work may also impact on researchers working in the pharmaceutical industry through the identification of potential new biomarkers (i.e. measurable indicators of some biological state or condition) and drug targets that can be exploited to aid disease diagnosis and treatment. There is also likely to be an impact on the third sector as we will seek to interact with relevant charities as our work progresses.

The outputs from this work will be maximised through a range of collaborations with other colleagues in the UK and overseas. We will collaborate with experts in a range of omics technologies (these are technologies used to explore the roles, relationships, and actions of the various types of molecules that make up the cells of an organism) to ensure that we develop a detailed understanding of molecular changes that are caused by deficits in our proteins of interest, and which may be linked to intellectual dysfunction.