Therapeutic target discovery and validation programme & the systems microscopy initiative
Lead Research Organisation:
University of Cambridge
Department Name: UNLISTED
Abstract
The discovery and development of new drugs for human diseases is a major scientific priority worldwide, but the process is beset with challenges that make it difficult, expensive and protracted. Our work exploits advances in our understanding of the molecular circuits controlling normal and diseased cells to identify and validate new targets for the next generation of medicines. We are also developing new methods for microscopy to better understand the effect of new medicines on diseased cells.
Technical Summary
There is a very high rate of attrition in the development of new classes of therapeutic agents that exploit our growing knowledge of the genetic basis of diseases like cancer, presenting a major impediment for academia and industry. Our ability to rapidly identify and validate of the best new therapeutic targets for drug development remains a a key challenge. To address this problem, we aim to build on the success of our recent work to develop novel approaches to systematically scrutinize cellular pathways altered in disease using large libraries encompassing diverse protein folds, and second, to extend using fragment-based and library-driven methods the discovery of chemical leads against novel molecular targets implicated in cellular regulation. In addition, our ongoing work to develop new approaches in light microscopy, such as hyper-dimensional imaging microscopy, to deconvolute complex cellular pathways will serve not only to advance understanding of disease-related derangements of these pathways, but also to validate diagnostic or therapeutic concepts for further development.
Organisations
Publications
Brear P
(2016)
Specific inhibition of CK2a from an anchor outside the active site.
in Chemical science
Briese M
(2019)
A systems view of spliceosomal assembly and branchpoints with iCLIP.
in Nature structural & molecular biology
Cassidy LD
(2014)
Chromosome instability and carcinogenesis: insights from murine models of human pancreatic cancer associated with BRCA2 inactivation.
in Molecular oncology
Cole D
(2017)
Computationally-guided optimization of small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction
in Chemical Communications
Cole DJ
(2017)
Computationally-guided optimization of small-molecule inhibitors of the Aurora A kinase-TPX2 protein-protein interaction.
in Chemical communications (Cambridge, England)
Related Projects
Project Reference | Relationship | Related To | Start | End | Award Value |
---|---|---|---|---|---|
MC_UU_12022/4 | 01/10/2013 | 31/03/2018 | £882,000 | ||
MC_UU_12022/5 | Transfer | MC_UU_12022/4 | 01/10/2013 | 31/03/2022 | £1,713,000 |
MC_UU_12022/6 | Transfer | MC_UU_12022/5 | 01/10/2013 | 31/03/2022 | £2,157,000 |
MC_UU_12022/7 | Transfer | MC_UU_12022/6 | 01/10/2013 | 31/03/2022 | £2,147,000 |
MC_UU_12022/8 | Transfer | MC_UU_12022/7 | 01/10/2013 | 31/03/2022 | £5,896,000 |
MC_UU_12022/9 | Transfer | MC_UU_12022/8 | 01/10/2014 | 31/03/2022 | £869,000 |
MC_UU_12022/10 | Transfer | MC_UU_12022/9 | 01/01/2015 | 31/03/2022 | £987,000 |
Description | Apollo - Aurora A |
Amount | £624,007 (GBP) |
Organisation | Apollo Therapeutics |
Sector | Private |
Country | United Kingdom |
Start | 11/2018 |
End | 01/2021 |
Description | MRC - A Joint Centre for Cancer Biology & Therapeutics (fellowships) |
Amount | £1,151,979 (GBP) |
Funding ID | MR/N501876/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2015 |
End | 04/2018 |
Description | Modulation of physiological and oncogenic Ras protein signaling via plasma membrane clustering |
Amount | £29,500 (GBP) |
Funding ID | IA/E/15/1/502339 |
Organisation | National Centre for Biological Science (NCBS) |
Sector | Academic/University |
Country | India |
Start | 04/2017 |
End | 03/2019 |
Description | Phoremost 2018 collab |
Amount | £8,094 (GBP) |
Organisation | PhoreMost |
Sector | Private |
Country | United Kingdom |
Start | 07/2018 |
End | 08/2019 |
Description | Sentinel Oncology |
Amount | £75,000 (GBP) |
Organisation | Sentinel Oncology |
Sector | Private |
Country | United Kingdom |
Start | 05/2018 |
End | 10/2018 |
Company Name | PhoreMost Limited |
Description | PhoreMost is a new-model drug discovery company based in Cambridge, UK: Using its core expertise to open up new 'druggable' target space and working with a global network of co-invested academic and industrial collaboration partners, we aim to bring a wide array of novel 'targeted' therapies more efficiently to market and pass these cost savings onto patients. |
Year Established | 2015 |
Impact | Advances in genomics and basic research are providing a long list of clear causes that lie at the heart of a range of debilitating diseases. This has the potential to open the door to many new and improved targeted therapies. However, many of these newly characterized disease targets are intractable to current drug discovery technologies. PhoreMost is aiming to remove these barriers to new drug development with its novel SITESEEKER technology, a live-cell phenotypic assay system that can rapidly identify unexpected, or "cryptic" druggable sites in specific disease driving targets and pathways that can't be readily seen using conventional non-cell based analytical methods. PhoreMost's first drug discovery program is based on a novel target that addresses the "undruggable" cancer gene KRAS, which affects multiple types of cancer. This program has recently completed lead optimisation and in vivo anti-tumour activity has been succesfully demonstrated. PhoreMost is now seeking partners for its further clinical development. |
Description | Cambridge Science Festival 2014 |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | Yes |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Group members spoke about their research and coordinated activities for the public such as DNA extraction. Increased awareness of cancer research and its importance. |
Year(s) Of Engagement Activity | 2014 |
Description | Festival Speaker Spotlight |
Form Of Engagement Activity | A magazine, newsletter or online publication |
Part Of Official Scheme? | Yes |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | Interviewed for Cambridge Science Festival Speaker Spotlight Increased awareness of cancer research and festival activities. |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.cam.ac.uk/science-festival/news-media/speaker-spotlights/speaker-spotlight-professor-asho... |
Description | Hosted Students from Hills Road 6th Form College, Cambridge |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Hosted students from Hills Road 6th Form College |
Year(s) Of Engagement Activity | 2019 |
Description | Interview on BBC Radio Cambridgeshire |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Interview on local radion Drivetime programme to discuss cancer research and promote cambridge science festival activities Increased awareness of research and attendance at festival event |
Year(s) Of Engagement Activity | 2014 |
Description | Participant 6th RNA Biology Symposium |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Participant 6th RNA Biology Symposium |
Year(s) Of Engagement Activity | 2020 |
Description | Participant: Early Detection conference |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Participant Early Detection conference |
Year(s) Of Engagement Activity | 2020 |
Description | Participant: LMB Lab Symposium October 2020 |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Participant: LMB Lab Symposium October 2020 |
Year(s) Of Engagement Activity | 2020 |
Description | Participant: NUS e-Open day |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Participant: NUS e-Open day |
Year(s) Of Engagement Activity | 2020 |
Description | Participation in AZ-CRUK Cambridge Centre Symposium |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Participation in AZ-CRUK Cambridge Centre Symposium |
Year(s) Of Engagement Activity | 2020 |