SSA - Innovative microscopy approaches to studying cellular senescence and regeneration in vivo.
Lead Research Organisation:
University of Sheffield
Department Name: Infection Immunity & Cardiovasc Disease
Abstract
We are all getting older and want a healthy retirement, but as increasing proportions of the population become older, there will be a substantial increase in the number of people affected by chronic diseases. We need to better understand how people age and find ways to help us age more healthily.
Stem cells interact with immune cells to determine tissue regeneration but as we age this becomes ineffective leading to reduced repair or loss of tissue function. We hypothesise that cells accumulate damage to a point where they are no longer able to work well and undergo a process called senescence. Existing models have been unable to address the precise role of senescent cells and their interaction with the immune system and how this affects regeneration.
Stem cells interact with immune cells to determine tissue regeneration but as we age this becomes ineffective leading to reduced repair or loss of tissue function. We hypothesise that cells accumulate damage to a point where they are no longer able to work well and undergo a process called senescence. Existing models have been unable to address the precise role of senescent cells and their interaction with the immune system and how this affects regeneration.
Studentship Projects
| Project Reference | Relationship | Related To | Start | End | Student Name |
|---|---|---|---|---|---|
| BB/M011151/1 | 01/10/2015 | 30/09/2023 | |||
| 1865323 | Studentship | BB/M011151/1 | 01/10/2015 | 30/09/2019 |
| Description | The amount of time that we spend alive (our lifespan) is increasing, but the time that we spend being healthy (our healthspan) is not. This means that we spend a greater proportion of our lives suffering from diseases, limiting our quality of life, our independence, and burdening health and social services. We know that ageing is the greatest risk factor for most diseases, and that when we are older, we often suffer from more than one disease at the same time. This means that we are treated with multiple medicines, which can work less well when used in combination. This has led to the idea that if we can understand why we develop multiple diseases with age and become less healthy, then we can take steps to tackle this and improve our healthspan, reducing the need to take multiple medicines. Recently, cellular senescence, a form of ageing in cells, has been shown to contribute to multiple diseases, such as Parkinson's, heart and joint diseases, when we are older. Drugs that remove these ageing cells are able to reduce the severity of these diseases and increase healthspan, but currently their side effects are limiting their effectiveness. We have developed a unique tool that uses zebrafish to identify improved drugs that remove ageing cells and don't have as many side effects. This is possible because in this specific zebrafish model, ageing cells fluoresce green, which means we can study them over time in a live animal. This allows us to understand where they are located, what other cell types they interact with, how long they last for, and whether drugs can efficiently remove them and improve the health of the zebrafish. This is the first time that this has been possible in the drug development process for improving healthspan. |
| Exploitation Route | We are currently testing compounds in our zebrafish, in collaboration with an SME in Vienna, to see whether we can truly better identify anti-ageing drugs with this model. We have numerous interested parties with compounds that they would like to test, and we have sent our zebrafish model out to multiple lab groups who intend to study senescence with it in various contexts. |
| Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
| Description | Testing of a new senolytic in a model of zebrafish senescence |
| Amount | £20,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 10/2019 |
| End | 02/2020 |
| Description | MRC Proximity to Discovery - grant to collaborate with an SME in Austria |
| Organisation | TAmiRNA GmbH |
| Country | Austria |
| Sector | Private |
| PI Contribution | We wrote and were successfully awarded a grant to test novel senolytic compounds in our newly developed zebrafish model. We have been testing these compounds for their efficacy, off-target toxicities, and changes in behaviour in zebrafish. |
| Collaborator Contribution | Providing knowledge and compounds to test in our new zebrafish model |
| Impact | Research is still ongoing, but results will help promote the zebrafish model to drug companies and should hopefully be used for publications and grants in future. |
| Start Year | 2019 |
| Description | Developing an ethics workshop around healthy ageing research, recruiting and facilitating researchers in taking part in my engagement activity, and evaluating how they went afterwards. |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | Ran two workshops on 'the ethics of healthy ageing research' to two sixth form schools - one locally in Cambridge (around 30 students) and another that visited from France (around 100 students). |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.babraham.ac.uk/blog/2019/01/my-time-as-a-public-engagement-intern-at-babraham-recommenda... |
| Description | Three month internship as Public Engagement Officer at Babraham Institute, Cambridge. Took part in Lifelab festival 2018. |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Ran engagement activities across two days in Peterborough and Cambridge city center, aimed at the public. Included lessons about model systems in ageing (c.elegans). 'Race against the clock' game to demonstrate the importance of lifestyle factors in healthy ageing. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.babraham.ac.uk/blog/2018/10/a-fish-out-of-water-how-a-zebra-fish-researcher-is-discoveri... |