Autophagy experts collaborate to hunt down potential drug targets to tackle neurodegeneration

Autophagy experts collaborate to hunt down potential drug targets to tackle neurodegeneration

Key points:

  • Nicholas Ktistakis joins researchers from the ALBORADA Drug Discovery Institute, and the MRC Mitochondrial Biology Unit on an ambitious project to find targets for neurodegeneration.
  • This collaboration is part of the Milner Consortium, an initiative to pair academics with pharmaceutical companies to fund projects into shared areas of interest.

A new collaboration from the Milner Consortium is bringing together academics across eminent Cambridge-based research groups to look for potential drug targets to treat a key process that could fight neurodegeneration – autophagy. Researchers from the Babraham Institute, the ALBORADA Drug Discovery Institute, and the MRC Mitochondrial Biology Unit will combine their expertise to pursue the most promising data in their search for targets. 

Over time the signals that keep us thinking and moving also lose their effect and connections between neurones are lost, leading to a number of neurodegenerative diseases like Parkinson’s and Alzheimer’s. At the same time, protein aggregates build up inside and outside of our brain cells which may be responsible for causing damage to neurones. In a healthy cell, these proteins would usually be dealt with by the autophagy pathway, which gathers damaged material for destruction. This new collaboration is looking for a way to understand why this pathway is less effective with age, and to see if we could ‘hack’ the pathway before these proteins make their way out of the cell – through the autophagy pathway.

There are lots of components and regulators in the autophagy pathway that make sure that the right material is gathered up and delivered to part of the cell that breaks them down. Signalling programme group leader Dr Nick Ktistakis has 15 years of experience investigating the autophagy pathway, and understanding the signals that feed into the pathway. The challenge facing this new collaboration is identifying the signals and regulators that help the cell to remove specific proteins associated with neurodegeneration.

Researchers have the best chances of making discoveries by working together and harnessing expertise from different groups. By working in parallel and exchanging findings, the collaborators can also improve the reproducibility of the research. “We have started by casting a wide net looking for targets. This way, we can collect data and validate findings before exploring the results that have the strongest chance of providing a good target”, Dr Ktistakis explained.

The Milner Consortium, formed in 2015, acts as a match maker for academics and pharmaceutical partners. Previous projects involving the Institute and other Milner Consortium partners include Simon Cook’s investigation into cancer cell growth. This latest project breaks the mould by connecting multiple academic groups with pharmaceutical partners in order to draw on expertise spanning autophagy and mitophagy (the autophagy pathway specifically for mitochondria).

For Dr Ktistakis, giving a talk at a Milner symposium was the starting point that led to this pioneering collaboration. Based on his talk, Nick was invited by the Milner Consortium together with other relevant academics, research organisations and pharmaceutical companies to an open agenda ‘sandpit’ workshop on autophagy. After further meetings and discussions, the key collaborators were selected.

“I felt well positioned to be a key player in this collaboration thanks to the support that my group receive at the Babraham Institute as a result of the capabilities and expertise within the Institute’s Imaging and Biological Chemistry facilities,” Dr Ktistakis explained. “The staff of our facilities are world experts in their fields who also have the ethos of enabling cutting edge work to be conducted by the research groups at the Institute. It is a truly unique environment.”

Notes to Editors

Contact
Honor Pollard, Communications Officer, honor.pollard@babraham.ac.uk

Image description
Left, Nick Ktistakis
Right, Human embryonic kidney cells treated with an autophagy activator and stained by immunofluorescence for two early autophagy proteins, WIPI2 (green) and FIP200 (red). 

Additional resources
Nick Ktistakis group pages
Nick Ktistakis's profile page
Milner Consortium news page
Simon Cook’s project “Investigating mechanisms of ERK1/2 inhibition”
Annual research report feature (2017): The quiet pathway

About the Babraham Institute
The Babraham Institute undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The Institute is strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation, through an Institute Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.

About BBSRC
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation, a non-departmental public body funded by a grant-in-aid from the UK government. BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond. Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20. We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.