Wellcome Trust MRC Human Inducible Pluripotent Stem Cell Initiative
Lead Research Organisation:
Wellcome Sanger Institute
Department Name: UNLISTED
Abstract
As it becomes cheaper and faster to sequence the DNA of individuals in the population we are faced with two challenges. One is to discover which aspects of the genetic variation between individuals are compatible with good health and which are linked to increased risk of specific diseases. The other is that it is not always obvious why a particular genetic mutation causes a particular disease; if we knew the answer we would be better placed to devise new ways to treat that disease. A technique that can help us meet these challenges is to make stem cells, known as induced pluripotent stem (iPS) cells, from small samples of the skin or blood of healthy and diseased individuals. By comparing the DNA of iPS cells with the way the cells behave when grown in the laboratory we can understand how variation in our DNA results in variation in cell behaviour and use this information to identify new disease mechanisms. The iPS cells and associated data that we generate will be freely available to researchers and doctors throughout the UK and will foster collaborations that will speed up the translation of research into improved diagnosis and treatment of disease.
Technical Summary
We will exploit the opportunities of the UK National Health Service to generate a national resource of human iPS cells and associated data. We will generate and bank lines from 700 healthy and 800 disease-associated individuals, optimising techniques for iPS cell production and quality control. Cells will be subjected to extensive analysis of genome, epigenome, gene expression and proteome. For cells from healthy individuals, in-depth analysis of inter-individual variability will provide an open access platform for association studies of cellular function, and for distinguishing pathological from physiological variation. Patient collections will be selected via an open call, focusing initially on well-characterised conditions, where a single genetic lesion underlies a pleiotropic clinical phenotype. To characterise cellular phenotype we will construct high throughput artificial microenvironments. We will evaluate cell death, differentiation, morphology and division and specific signalling pathways. We will collaborate to produce protocols to differentiate iPS cells into disease-relevant cell types. These approaches will provide in vitro readouts of inter-individual variation and disease and a platform for gene correction and engineering specific mutations into different genetic backgrounds. Our proposal will give researchers in the UK and beyond access to iPS cells and technology linked to extensive genetic, cellular and clinical information.
Organisations
People |
ORCID iD |
Fiona Watt (Principal Investigator) | |
Richard Durbin (Co-Investigator) |
Publications
Alasoo K
(2018)
Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response.
in Nature genetics
Clarke G
(2018)
Bench to bedside: Current advances in regenerative medicine.
in Current opinion in cell biology
Di Angelantonio E
(2017)
Body-mass index and all-cause mortality - Authors' reply.
Description | Impact of missense mutations in recessive Mendelian disease: insight from ciliopathies |
Amount | £206,112 (GBP) |
Funding ID | 210585/C/18/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 12/2018 |
End | 09/2023 |
Description | Advice for applicants for Wellcome Trust Sir Henry Dale Fellowships http://elifesciences.org/elife-news/webinar-report-Sir-Henry-Dale |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other audiences |
Results and Impact | Advice to postdocs on obtaining a career development award. |
Year(s) Of Engagement Activity | 2016 |
URL | http://elifesciences.org/elife-news/webinar-report-Sir-Henry-Dale |
Description | Hay Literary Festival |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Inaugural Rosalind Franklin lecture on behalf of King's College London at Hay Festival. Topic: stem cell research. Generated national media interest. |
Year(s) Of Engagement Activity | 2013 |
Description | Interview on Korean radio |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Interview on UK stem cell research for South Korean live radio programme 'Primetime with Henry Shinn' (http://www.tbs.seoul.kr/efm/Primetime) Explained UK stem cell research to an international community. |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.tbs.seoul.kr/efm/Primetime |
Description | Interview with Times Higher Education (issue number 2,077) on optimal laboratory size |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Quoted in article. Stimulated debated. |
Year(s) Of Engagement Activity | 2013 |
Description | Pint of Science |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Local |
Primary Audience | Media (as a channel to the public) |
Results and Impact | May 2013: speaker, ' A Pint of Science' festival (http://www.pintofscience.com). Discussion about stem cell research with members of the public. Lay interest in research. |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.pintofscience.com |
Description | Stem Cell Research: From Utopian Dream to Reality (2016) https://www.youtube.com/watch?v=JIqULf7xJ90&feature=em-subs_digest |
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 | Exhibition and video as part of 'Utopia 2016' exhibition at Somerset House. |
Year(s) Of Engagement Activity | 2016 |
URL | http://www.youtube.com/watch?v=JIqULf7xJ90&feature=em-subs_digest |
Description | radio interviews |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Gave interviews for BBC Radio 5 Live and the Today programme on report of stem cell therapy for stroke victims; June 2013 Stimulated public interest in stem cell research. |
Year(s) Of Engagement Activity | 2013 |
Description | short movie about stem cell research |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Made video about stem cell research for KCL website; July 2013 Members of my lab participated. |
Year(s) Of Engagement Activity | 2013 |