Salford Institute for Dementia

Research theme: Extraordinary

Title of research project/activity

  1. Investigating alterations in autophagy in frontotemporal lobar degeneration
  2. Exploring protein degradation deficits in Alzheimer’s disease

Team members and School(s)/other institutions involved

ELS: Gemma Lace-Costigan (PI), Lucy Smyth (co-supervisor), Niroshini Nirmalan (co-supervisor), Richard Heale (Project 1 PhD student), Diana Stan (Project 2 PhD student) University of Manchester/Salford Royal: David Mann and Andrew Robinson (Collaborators)

Funding bodies/amount:

  1. ARUK (£80,467 PhD studentship grant)
  2. ARUK Local Network Equipment grant (2014 £1400, 2015/16 £3000)

Start date:

  1. October 2015
  2. October 2014

End date:

  1. October 2019
  2. October 2018

Overview of research aims and selected highlights

The accumulation of abnormal proteins and associated cell death is a feature of numerous neurodegenerative disorders, including Alzheimer’s disease, frontotemporal dementia, Parkinson’s disease and motor neurone disease. The increased accumulation of these abnormal proteins has been shown to be associated with increased cognitive impairment and brain cell death, so preventing the build up of these proteins is a potential therapeutic strategy.

There have recently been a number of animal and cellular based studies that have identified deficits in the systems that usually serve to degrade and prevent the accumulation of damaged cellular components and abnormal proteins. However, the exact nature of these problems is poorly understood and there is limited research involving human brain tissue. Our group aims to explore alterations in the different protein degradation pathways (such as autophagy and the ubiquitin proteasome system) in different dementia associated diseases such as Alzheimer’s disease and frontotemporal dementia. Using human brain tissue for the

Manchester brain bank and cell culture based disease models our research aims to identify which parts of these complex protein clearance pathways are abnormal in disease and identify novel targets for therapeutic intervention.

Progress to date

Project 1 has been running for 4 months and project 2 has been running 1 year and 4 months

Outputs (papers, book chapters, conference presentations, poster presentations etc)

Oral Presentations

Lace-Costigan, GL, Stan DM (2015). Exploring chaperone mediated autophagy in the human hippocampus. Presented at the Alzheimer’s Research UK North West Science Day

Stan, DM. Exploring autophagy deficits in human brain tissue and skin derived fibroblasts

(2015). Presented at the Alzheimer’s Research UK PhD and Post-Doc Networking Event Heale, R. Investigating protein degradation pathway deficits in frontotemporal dementia (2015). Presented at the Alzheimer’s Research UK PhD and Post-Doc Networking Event

Future plans arising from activity

Invited oral presentation at the National Alzheimer’s Research UK PhD Student Day by

Gemma Lace-Costigan (March 2016)

Accepted poster presentation at the National Alzheimer’s Research UK PhD Student Day by

Diana Stan (March 2016)

The work of projects 1 and 2 is anticipated to generate enough data for at least four high impact journal publications. Additionally, the data collected in these research projects will be used in a major grant application which will aim to secure funding for a project to explore therapeutic mechanisms of enhancing protein clearance in neurodegenerative diseases.

Impacts (or anticipated impacts) and/or engagement activities

Gemma Lace-Costigan was an invited speaker at the ‘Alzheimer’s Disease: An Afterthought?’ event as part of the Manchester Science Festival 2015.

The work of the group received media attention after a Alzheimer’s Research UK press release in 2015 where the research was presented and discussed on BBC Radio Manchester an in a number of local papers.

Gemma Lace-Costigan, Diana Stan and Richard Heale were part of the Alzheimer’s Research UK Park Run ‘Donate Your Time’ campaign. They attended and completed a 5K park run and raised awareness of dementia research.

Richard Heale is planning on applying for the ‘Brilliant Club’ which is a charity that recruits, trains and pays doctoral and post-doctoral researchers to deliver programmes of university-style teaching to small tutorial groups of high-performing pupils in schools that serve communities with a low participation rate in Higher Education. He will use this opportunity to bring dementia awareness to children and teachers within schools.

Gemma Lace-Costigan, Richard Heale, Diana Stan and a team of undergraduate volunteers will be representing the University of Salford at a ECoS neuroscience event called ‘The Brain Box’ which will take place in the Town Hall on Manchester Day (19th June 2016). The team will lead a number of creative activities which will focus on brain anatomy and physiology with an aim to improve the general understanding of the brain and introduce younger audiences to how the brain is affected in dementia.

Contact

Gemma Lace-Costigan

Email: g.l.lace-costigan@salford.ac.uk

Tel. 0161 295 5111