A Translational Research Resource Centre and Image-Based Screening Platform for MRC-LMCB, UCL.
Lead Research Organisation:
MRC Laboratory of Molecular Biology
Department Name: UNLISTED
Abstract
We propose to establish a Translational Research Resource Centre at the MRC-Laboratory for Molecular Biology/Cell Biology Unit (LMCB/CBU) that will provide know-how and technical platforms for the MRC, UCL and the surrounding research community to facilitate and develop the translation of basic research. The initial platform will be an automated image-based high through-put screening system, coupled with the technique of RNA interference (RNAi), which has now become one of the most powerful methods for identifying genes/proteins involved in a variety of cellular pathways and pathological conditions. The same assays and equipment can be used to screen small compound libraries, thus allowing not only the identification of novel targets for drug development but also lead compounds for a range of genetic and infectious diseases as well as conditions such as cancer, neuro-degeneration and visual failure. Major programmes of this sort are already underway elsewhere in Europe and the USA. Our program will bring these key new technologies to the MRC and the UCL communities - one of the largest concentrations of biomedical research in the UK.
Technical Summary
We propose to establish a Translational Research Resource Centre in the MRC-Laboratory for Molecular Biology/Cell Biology Unit that exploits our expertise in cell biology and imaging to enhance and develop the translation of basic biomedical research to applications. The Centre will provide a resource for the MRC, UCL and other local/affiliated institutions through which expert partners can be found to link basic research to identified human disease candidates. The MRC-LMCB is well placed to provide the expert skills and the technical resource base to make these links. The three main goals will be: -
1) To facilitate translation of basic research outcomes
2) To provide expert research and technical resources to determine the mechanism /function of identified candidates in human disease
3) To implement emerging technologies to enhance translational research outcomes
An initial technical platform to support these activities will be a fully automated high through-put image-based screening system for RNAi and small compound libraries to identify novel drug targets and lead compounds relevant for a range of conditions and diseases including infectious disease (HIV), cancer growth, metastasis and invasion, visual failure, neural degeneration and genetic disease, inflammation, haemostasis, and metabolic diseases. A number of these platforms have been established in the USA and elsewhere in Europe but have not been developed extensively in the UK and are not available within UCL or the MRC.
1) To facilitate translation of basic research outcomes
2) To provide expert research and technical resources to determine the mechanism /function of identified candidates in human disease
3) To implement emerging technologies to enhance translational research outcomes
An initial technical platform to support these activities will be a fully automated high through-put image-based screening system for RNAi and small compound libraries to identify novel drug targets and lead compounds relevant for a range of conditions and diseases including infectious disease (HIV), cancer growth, metastasis and invasion, visual failure, neural degeneration and genetic disease, inflammation, haemostasis, and metabolic diseases. A number of these platforms have been established in the USA and elsewhere in Europe but have not been developed extensively in the UK and are not available within UCL or the MRC.
Organisations
- MRC Laboratory of Molecular Biology (Lead Research Organisation)
- European Cooperation in Science and Technology (COST) (Collaboration)
- Eisai Ltd (Collaboration)
- Aligning Sciences Across Parkinson's (Collaboration)
- AstraZeneca (Collaboration)
- UNIVERSITY OF ABERDEEN (Collaboration)
- RIKEN (Collaboration)
- MRC-Technology (Collaboration)
- British Columbia Cancer Agency (BCCA) (Collaboration)
- Pasteur Institute, Paris (Collaboration)
- Horizon Genomics (Collaboration)
- Government of Wales (Collaboration)
- UNIVERSITY OF LEEDS (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- Perkin Elmer (Collaboration)
- Agency for Science, Technology and Research (A*STAR) (Collaboration)
- Cellular Dynamics (Collaboration)
- Samsara Therapeutics (Collaboration)
- University of Copenhagen (Collaboration)
- University College London (Collaboration)
- UNIVERSITY OF NOTTINGHAM (Collaboration)
- Thermo Fisher Scientific (United Kingdom) (Collaboration)
- IMPERIAL COLLEGE LONDON (Collaboration)
- Cancer Research UK (Collaboration)
- Institute of Cancer Research UK (Collaboration)
- Johnson & Johnson (Collaboration)
- University of Toronto (Collaboration)
- University of Antwerp (Collaboration)
People |
ORCID iD |
Mark Marsh (Principal Investigator) |
Publications
Heintze J
(2016)
Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy.
in Cellular signalling
Heintze J
(2016)
Ribose 5-phosphate isomerase inhibits LC3 processing and basal autophagy.
in Cellular signalling
Kriston-Vizi J
(2017)
Getting the whole picture: High content screening using three-dimensional cellular model systems and whole animal assays.
in Cytometry. Part A : the journal of the International Society for Analytical Cytology
Kriston-Vizi J
(2017)
Getting the whole picture: High content screening using three-dimensional cellular model systems and whole animal assays.
in Cytometry. Part A : the journal of the International Society for Analytical Cytology
Matthews HK
(2012)
Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression.
in Developmental cell
Matthews HK
(2012)
Changes in Ect2 localization couple actomyosin-dependent cell shape changes to mitotic progression.
in Developmental cell
Ferraro F
(2014)
A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells.
in Developmental cell
Ferraro F
(2014)
A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells.
in Developmental cell
Description | Document on the implications of Brexit on research funding at UCL |
Geographic Reach | Europe |
Policy Influence Type | Contribution to a national consultation/review |
Description | Member of COVID19 emergency team at the LMCB |
Geographic Reach | Local/Municipal/Regional |
Policy Influence Type | Membership of a guideline committee |
Impact | The COVID19 emergency team provides guidance on access to the LMCB research laboratories and institute during the COVID19 pandemic. The panel facilitated the well-being of staff and access to research and education. |
Description | Membership of Advisory Panel UCL-Eisai Collaboration |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Michael J Fox Foundation Parkin Consortium |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Description | Michael J Fox Foundation Parkin Consortium |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Description | NBIA Disorders Medical and Scientific Advisory Board |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
Impact | We have generated questionnaires for carers of NBIA patients and made recommendations for care. |
Description | Scientific Advisor to AstraZeneca High-Content Biology |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | Scientific Advisor to AstraZeneca High-Content Biology |
Geographic Reach | Europe |
Policy Influence Type | Participation in a guidance/advisory committee |
Description | The Royal Society Newton Fellowship panel member |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Membership of a guideline committee |
Description | Action Medical Research PhD Fellowship |
Amount | £230,000 (GBP) |
Organisation | Action Medical Research |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2016 |
End | 08/2018 |
Description | BBSRC |
Amount | £352,900 (GBP) |
Funding ID | BB/L021404/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | |
End | 09/2017 |
Description | BBSRC New Investigator Scheme |
Amount | £255,375 (GBP) |
Funding ID | BB/JO15881/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2013 |
End | 12/2015 |
Description | Capital Equipment Fund, CEF3 |
Amount | £500,000 (GBP) |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 07/2019 |
End | 07/2020 |
Description | Dementia Platform UK |
Amount | £1,900,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 03/2015 |
End | 03/2016 |
Description | Dissecting the mechanisms underlying disease progression in parkinsonism |
Amount | £7,014,337 (GBP) |
Funding ID | ASAP-000478 |
Organisation | Aligning Sciences Across Parkinson's |
Sector | Charity/Non Profit |
Country | United States |
Start | 03/2021 |
End | 03/2024 |
Description | Drugs4Targets |
Amount | € 5,000 (EUR) |
Organisation | Bayer |
Department | Bayer HealthCare |
Sector | Private |
Country | Germany |
Start | 07/2012 |
End | 07/2013 |
Description | EU FP7 Innovative Medicines |
Amount | € 6,000,000 (EUR) |
Funding ID | HIVINNOV |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | |
End | 10/2015 |
Description | EU Marie-Curie Reintegration Fund |
Amount | € 50,000 (EUR) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 03/2011 |
End | 03/2013 |
Description | Eisai-UCL Collaboration Project TIG E |
Amount | £231,000 (GBP) |
Organisation | Eisai Ltd |
Sector | Private |
Country | Japan |
Start | 11/2017 |
End | 04/2020 |
Description | Enhanced mitophagy as therapeutic opportunity in Parkinsons disease |
Amount | £256,201 (GBP) |
Funding ID | TIG F |
Organisation | Eisai Ltd |
Sector | Private |
Country | Japan |
Start | 04/2020 |
End | 04/2022 |
Description | High-Throughput Electroporation of Primary Cells |
Amount | £85,000 (GBP) |
Funding ID | 101472 |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2013 |
End | 07/2014 |
Description | Lysosome Function Enhancement to Treat Synucleinopathies |
Amount | £384,000 (GBP) |
Funding ID | TIG G |
Organisation | Eisai Ltd |
Sector | Private |
Country | Japan |
Start | 03/2020 |
End | 03/2022 |
Description | MRC Centre for Medical and Molecular Virology |
Amount | £2,778,000 (GBP) |
Funding ID | G0900950 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | |
End | 11/2014 |
Description | Marie-Curie International Incoming Fellow |
Amount | € 221,606 (EUR) |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Sector | Public |
Country | European Union (EU) |
Start | 03/2014 |
End | 03/2016 |
Description | Michael J Fox Foundation |
Amount | $78,000 (USD) |
Organisation | Michael J Fox Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2014 |
End | 12/2014 |
Description | Michael J Fox Foundation |
Amount | $78,000 (USD) |
Organisation | Michael J Fox Foundation |
Sector | Charity/Non Profit |
Country | United States |
Start | 01/2014 |
End | 12/2014 |
Description | Multi-user equipment grant |
Amount | £85,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2013 |
End | 05/2015 |
Description | New Investigator Scheme |
Amount | £252,797 (GBP) |
Funding ID | BB/J015881/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start |
Description | Small molecule inhibition of ATG4B for therapeutic strategies in pancreatic ductal adenocarcinoma |
Amount | £75,000 (GBP) |
Funding ID | 557595 |
Organisation | University College Hospital |
Sector | Hospitals |
Country | United Kingdom |
Start | 03/2021 |
End | 02/2022 |
Description | TDRF |
Amount | £151,213 (GBP) |
Funding ID | BB/P027431/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2018 |
End | 02/2019 |
Description | Targeting autophagy dependence in pancreatic cancer |
Amount | £109,341 (GBP) |
Funding ID | 2018RIF_15 |
Organisation | Pancreatic Cancer UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 08/2019 |
End | 09/2023 |
Description | UCL Capital Investment Fund |
Amount | £150,000 (GBP) |
Funding ID | FK20 |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2010 |
End | 12/2011 |
Description | UCL Capital Investment Fund |
Amount | £150,000 (GBP) |
Organisation | University College London |
Department | School of Life and Medical Sciences |
Sector | Academic/University |
Country | United Kingdom |
Start | 01/2010 |
End | 12/2010 |
Description | UCL Confidence in Concept Award |
Amount | £99,208 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2014 |
End | 05/2015 |
Description | UCL Confidence in Concept Award |
Amount | £99,753 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2013 |
End | 05/2014 |
Description | UCL Eisai collaboration |
Amount | £5,000,000 (GBP) |
Organisation | Eisai Ltd |
Sector | Private |
Country | Japan |
Start | 11/2017 |
End | 04/2019 |
Description | UCL MRC Confidence in Concepts |
Amount | £99,753 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2013 |
End | 05/2014 |
Description | UCL MRC Confidence in Concepts |
Amount | £99,208 (GBP) |
Organisation | Medical Research Council (MRC) |
Department | MRC Confidence in Concept Scheme |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 05/2014 |
End | 05/2015 |
Description | UCL Therapeutic Innovation Fund |
Amount | £50,000 (GBP) |
Funding ID | FKHM |
Organisation | University College London |
Sector | Academic/University |
Country | United Kingdom |
Start | 05/2010 |
End | 05/2011 |
Description | UCL-Eisai Collaboration |
Amount | £12,500 (GBP) |
Organisation | Eisai Ltd |
Sector | Private |
Country | Japan |
Start | 09/2016 |
End | 03/2017 |
Description | University of Pennsylvania Orphan Disease Center |
Amount | $51,020 (USD) |
Funding ID | MDBR-19-102-BPAN |
Organisation | University of Pennsylvania |
Sector | Academic/University |
Country | United States |
Start | 02/2019 |
End | 01/2020 |
Description | WT Institutional Strategic Support Fund |
Amount | £65,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2015 |
End | 12/2017 |
Description | WT Multi-user equipment grant |
Amount | £170,000 (GBP) |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 07/2013 |
End | 07/2014 |
Title | ATG4 Knockout cell lines |
Description | HeLa cell lines with knockout of ATG4A, B and C, generated by CRISPR/Cas9 genome editing. |
Type Of Material | Cell line |
Year Produced | 2019 |
Provided To Others? | Yes |
Impact | New insights into ATG4 biology that has led to collaborations with pharmaceutical partners. |
Title | ATG4ABC CRISPR knockout cell line |
Description | HeLa cells with knockout of three proteins (ATG4A, B and C) generated by CRISPR/Cas9 genome editing |
Type Of Material | Cell line |
Year Produced | 2018 |
Provided To Others? | Yes |
Impact | This cell line will be useful for further research into the function of ATG4 proteases and can be used in early stage drug discovery for target validation. |
Title | Induced pluripotent stem cells from patients with BPAN disease |
Description | We generated human induced pluripotent stem cells from patients with BPAN disease. |
Type Of Material | Model of mechanisms or symptoms - human |
Year Produced | 2019 |
Provided To Others? | No |
Impact | We are currently screening small molecule libraries to identify potential hit compounds with therapeutic benefit. The cells are available upon request. |
Title | Inhibitor and activator compounds of ATG4B protease. |
Description | We have identified inhibitors, as well as activators of the autophagy protease ATG4B. |
Type Of Material | Technology assay or reagent |
Year Produced | 2018 |
Provided To Others? | No |
Impact | These compounds have therapeutic potential and we are further developing them into lead compounds for the treatment of cancer. |
Title | Inhibitor compounds of CLK2 kinase |
Description | We have identified chemical probes that inhibit proteins of the CLK2 family of proteins. |
Type Of Material | Technology assay or reagent |
Year Produced | 2016 |
Provided To Others? | Yes |
Impact | The CLK2 inhibitors will provide useful tools to study the function of these proteins and can be used in drug discovery. |
Title | Modified luciferase release assay |
Description | This new version of a luciferase-based assay to monitor autophagy protease ATG4 activity can be used in academic research and drug target identification. The new version includes assays to monitor other protein targets of ATG4, such as LC3A and mutants thereof. |
Type Of Material | Technology assay or reagent |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | We have given the plasmid encoding this reporter to several other research groups. We are actively sharing this reagents with multiple labs and hope that this will advance research in this field. |
Title | Analysis pipeline for morphometric analysis of high-content screening data |
Description | This is an image analysis workflow designed for the analysis of large-scale data of high-content imaging data. |
Type Of Material | Data analysis technique |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | The workflow was published alongside the full data. The full data was downloaded over 100 times for re-analysis and further data generation. |
URL | https://www.nature.com/articles/sdata201722 |
Description | ARUK DDI |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The UKDP is working closely with the ARUK Drug Discovery Institute with the aim to develop novel therapies for neurodegenerative disorders. Both networks collaborate closely in terms of drug discovery research and through exchange of knowledge, equipment and technologies. |
Collaborator Contribution | The UKDP is working closely with the ARUK Drug Discovery Institute with the aim to develop novel therapies for neurodegenerative disorders. Both networks collaborate closely in terms of drug discovery research and through exchange of knowledge, equipment and technologies. |
Impact | None yet |
Start Year | 2017 |
Description | ASAP Consortium |
Organisation | Aligning Sciences Across Parkinson's |
Country | United States |
Sector | Charity/Non Profit |
PI Contribution | Provision of assays and expertise |
Collaborator Contribution | Shared Postdoc |
Impact | Collaboration network |
Start Year | 2021 |
Description | ATG4B compounds BC Cancer Agency |
Organisation | British Columbia Cancer Agency (BCCA) |
Country | Canada |
Sector | Public |
PI Contribution | We are assaying compounds that inhibit autophagy in our cell-based assays. |
Collaborator Contribution | Provision of chemical compounds for testing. |
Impact | No outcomes yet. |
Start Year | 2014 |
Description | Adhiron-based inhibitors of Grb2 signaling |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are studying Grb2-mediated signaling pathways using non-antibody based inhibitors. |
Collaborator Contribution | Provision of non-antibody based binding proteins of Grb2. |
Impact | No outputs yet. |
Start Year | 2013 |
Description | Arrayed CRISPR Library Screening |
Organisation | Thermo Fisher Scientific |
Country | United States |
Sector | Private |
PI Contribution | We are developing protocols for arrayed CRISPR library screening in partnership with ThermoFisher. |
Collaborator Contribution | ThermoFisher has provided us with early access to a lentivirus library that is not yet commercially available. Also, Thermofisher is providing consumables and reagents for this research project. |
Impact | We are currently preparing experiments for publication. Also, a Postdoc in the lab has presented preliminary results at the Wellcome Trust-AstraZeneca CRISPR conference in January 2016. Further, I have been invited to present these data at the CRISPR conference in Oxford in April 2016 and the GE/Dharmacon Functional Genomics meeting in London in April 2016. |
Start Year | 2015 |
Description | Arrayed CRISPR library screening |
Organisation | Thermo Fisher Scientific |
Country | United States |
Sector | Private |
PI Contribution | "We are developing protocols for arrayed CRISPR library screening in partnership with ThermoFisher." |
Collaborator Contribution | "ThermoFisher has provided us with early access to a lentivirus library that is not yet commercially available. Also, Thermofisher is providing consumables and reagents for this research project." |
Impact | "We are currently preparing experiments for publication. Also, a Postdoc in the lab has presented preliminary results at the Wellcome Trust-AstraZeneca CRISPR conference in January 2016. Further, I have been invited to present these data at the CRISPR conference in Oxford in April 2016 and the GE/Dharmacon Functional Genomics meeting in London in April 2016." |
Start Year | 2015 |
Description | CDI |
Organisation | Government of Wales |
Department | Cadw |
Country | United Kingdom |
Sector | Public |
PI Contribution | Provision of cell-based assays for autophagy. |
Collaborator Contribution | Provision of induced pluripotent stem cell-derived neurons for the development of autophagy assays. |
Impact | Research data being generated. |
Start Year | 2012 |
Description | COST Action Proteocure |
Organisation | European Cooperation in Science and Technology (COST) |
Country | Belgium |
Sector | Public |
PI Contribution | Sharing expertise and data. |
Collaborator Contribution | Workshops, Conferences |
Impact | This is a European network to study the role of proteases in various diseases. |
Start Year | 2021 |
Description | CRISPR Core Facility Copenhagen |
Organisation | University of Copenhagen |
Country | Denmark |
Sector | Academic/University |
PI Contribution | Hosted a Postdoctoral researcher from the CRISPR Core Facility at the University of Copenhagen to train her in arrayed CRISPR screening methods. |
Collaborator Contribution | Shared protocols and assays. |
Impact | Training of a skilled researcher. |
Start Year | 2022 |
Description | Cellular Dynamics International |
Organisation | Cellular Dynamics |
Country | United States |
Sector | Private |
PI Contribution | Expertise in high-content screening of primary neurons |
Collaborator Contribution | Provision of iPS-derived neurons. |
Impact | None to date. |
Start Year | 2012 |
Description | Chemistry of ATG4B Inhibitors |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have developed cell-based and in vitro assays to monitor autophagy protease activity. We work with researchers at UCL for provision of chemical libraries and chemistry to enable drug discovery projects. |
Collaborator Contribution | Provision of chemical compounds and expertise in chemistry. |
Impact | This partnership is multi-disciplinary and involves chemistry, biology and bioinformatics. |
Start Year | 2014 |
Description | Darren Tomlinson, University of Leeds |
Organisation | University of Leeds |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Assays for EGFR/Grb2 signaling and binding studies |
Collaborator Contribution | Provision of non-antibody binding protein inhibitors of Grb2 |
Impact | None to date |
Start Year | 2013 |
Description | David Selwood, UCL |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Small molecule screening and drug discovery |
Collaborator Contribution | Provision of small molecule library Chemibank |
Impact | None to date |
Start Year | 2010 |
Description | Developing a 3D model for pancreatic cancer |
Organisation | University College London |
Department | Division of Surgery & Interventional Science |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This collaboration has enabled us to jointly develop novel three-dimensional tumour in a dish models for pancreatic cancer. |
Collaborator Contribution | The partners have developed an innovative methods to generate 3D spheroids on a scaffold, which allows us to perform complex staining procedures in a three-dimensional model of PDAC. |
Impact | None so far. |
Start Year | 2021 |
Description | Dr Marcus Dorner, Imperial College |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided data and expertise on the effect of Hsp90 on regulation of HIV-1 latency, provided specific Hsp90 inhibitor. |
Collaborator Contribution | humanized mouse models for HIV-1 infection to test the effect of selective Hsp90 inhibitors on HIV-1 latency. |
Impact | experiments ongoing. |
Start Year | 2014 |
Description | Dr. Lee Hwee Kuan |
Organisation | Agency for Science, Technology and Research (A*STAR) |
Department | Bioinformatics institute (BII) |
Country | Singapore |
Sector | Academic/University |
PI Contribution | Joint supervision of William Grimes PhD student with Prof Dan Cutler |
Collaborator Contribution | Joint supervision and provides Singapore International Graduate Award (SINGA) for PhD student William Grimes. |
Impact | n/a |
Start Year | 2013 |
Description | Dr. Peter Cherepanov, CRUK |
Organisation | Cancer Research UK |
Country | United Kingdom |
Sector | Charity/Non Profit |
PI Contribution | Provision of expression constructs, recombiinant protein expression vectors and methods for immunoprecipitation. Expertise on nuclear transport receptors. |
Collaborator Contribution | Structural biology of Transportin 3 |
Impact | one paper in PNAS: Maertens, G. N., Cook, N. J., Wang, W., Hare, S., Gupta, S. S., Oztop, I., Lee, K., Pye, V. E., Cosnefroy, O., Snijders, A. P., Kewalramani, V. N., Fassati, A., Engelman, A., Cherepanov, P. (2014). Structural basis for nuclear import of splicing factors by human Transportin 3. Proc Natl Acad Sci U S A doi:10.1073/pnas.1320755111. Author URL Zaitseva, L., Cherepanov, P., Leyens, L., Wilson, S. J., Rasaiyaah, J., Fassati, A. (2009). HIV-1 exploits importin 7 to maximize nuclear import of its DNA genome. Retrovirology 6, 11- doi:10.1186/1742-4690-6-11. |
Start Year | 2010 |
Description | Dr. Richard Benarous, Mutabilis, France |
Organisation | University College London |
Department | Metbolism and Endocrinology |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Performed novel high through put screening to identify host factors necessary for HIV-1 replication. |
Collaborator Contribution | Provided expertise and library of 10,000 small chemical compounds selected from a 150,000 compounds library. |
Impact | Identified four new compounds with antiretroviral activity: they belong to a new class of antiretrovirals. |
Start Year | 2012 |
Description | Dr. Veronique Birault, GSK, Stevenage |
Organisation | GlaxoSmithKline (GSK) |
Country | Global |
Sector | Private |
PI Contribution | Provided data on a new host factor to be used as an antiretroviral target with novel mechanism of action. |
Collaborator Contribution | Provided lead compounds that target the new host factor discovered by us. |
Impact | In the process of performing SAR studies with GSK compounds |
Start Year | 2013 |
Description | Eisai Pharmaceuticals |
Organisation | Eisai Ltd |
Department | Eisai Europe Ltd |
Country | United Kingdom |
Sector | Private |
PI Contribution | expertise in HTS of autophagy/mitophagy |
Collaborator Contribution | Provision of cDNA library and small molecule compounds |
Impact | None |
Start Year | 2013 |
Description | Eisai Pharmaceuticals |
Organisation | Eisai Ltd |
Country | Japan |
Sector | Private |
PI Contribution | In collaboration with researchers at Eisai and funded through the Michael J Fox Foundation, we are exploring the role of De-ubiquitinating enzymes in Parkin-mediated mitophagy. We are providing the underlying cell biology for this study. |
Collaborator Contribution | Provision of a cDNA library and expertise in the field of neuro-degeneration. This has led to funding from the Michael J Fox Foundation for a pilot project. Since 2017, the partner has provided substantial funding for an early stage drug discovery project in my lab. This project has been initiated in 2017 and is ongoing. |
Impact | This collaboration has led to two successful funding applications. One is with the Michael J Fox Foundation. The other is with the industry partner itself, which is funding an early stage drug discovery project and a Postdoctoral scientist in the lab. |
Start Year | 2013 |
Description | ICR Kirkin |
Organisation | Institute of Cancer Research UK |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | This is a research collaboration, which is lead by my team at UCL. |
Collaborator Contribution | The collaborator has given us access to important research tools and reagents and will contribute by performing in vivo studies in the future. |
Impact | None so far |
Start Year | 2018 |
Description | Johnson & Johnson |
Organisation | Johnson & Johnson |
Country | United States |
Sector | Private |
PI Contribution | We are screening a small molecule library from J&J with the aim to identify tool compounds that modulate breast cancer cell growth and autophagy. |
Collaborator Contribution | We have received a small molecule library targeting cysteine proteases for screening. |
Impact | Exchange of know-how and materials. |
Start Year | 2017 |
Description | Knockout Cell Panel Screening |
Organisation | Horizon Genomics |
Country | United Kingdom |
Sector | Private |
PI Contribution | We are developing protocols for the use of CRISPR-engineered knockout cell panels in arrayed screening. |
Collaborator Contribution | Provision of knockout cell lines and knockout cell panels free of charge. |
Impact | We are preparing experiments for publication. |
Start Year | 2015 |
Description | Knockout Cell Panel Screening |
Organisation | Horizon Genomics |
Country | United Kingdom |
Sector | Private |
PI Contribution | "We are developing protocols for the use of CRISPR-engineered knockout cell panels in arrayed screening." |
Collaborator Contribution | "Provision of knockout cell lines and knockout cell panels free of charge." |
Impact | "We are preparing experiments for publication." |
Start Year | 2015 |
Description | MRC-T |
Organisation | MRC-Technology |
Country | United Kingdom |
Sector | Private |
PI Contribution | Small molecule screening and drug discovery |
Collaborator Contribution | Provision of small molecule library |
Impact | None to date |
Start Year | 2010 |
Description | MRCT Index Compound Set |
Organisation | MRC-Technology |
Country | United Kingdom |
Sector | Private |
PI Contribution | High-throughput screening of small molecule compounds |
Collaborator Contribution | Provision of small molecule library |
Impact | None to date |
Start Year | 2015 |
Description | MRCT Index Compound Set |
Organisation | MRC-Technology |
Country | United Kingdom |
Sector | Private |
PI Contribution | High-throughput screening of small molecule compounds" |
Collaborator Contribution | "Provision of small molecule library" |
Impact | None to date |
Start Year | 2015 |
Description | MaMTH EGFR Interactions |
Organisation | University of Toronto |
Country | Canada |
Sector | Academic/University |
PI Contribution | We are studying novel interaction partners of the EGFR that were identified using a technology developed in Igor Stagljar's lab at University of Toronto. |
Collaborator Contribution | Access to MaMTH, a novel method to identify protein-protein interactions. |
Impact | A publication has been published: Petschnigg et al. J Mol Biol 2017. |
Start Year | 2014 |
Description | Marcel Jaspars, Univ Aberdeen |
Organisation | University of Aberdeen |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Small molecule screening and drug discovery |
Collaborator Contribution | Provision of small molecule library, marine natural products |
Impact | None to date |
Start Year | 2012 |
Description | Medicinal Chemistry of Autophagy modulators |
Organisation | University College London |
Department | School of Pharmacy |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | "Testing small molecule compounds generated by the School of Pharmacy in autophagy assays." |
Collaborator Contribution | "Generation and provision of 26 compounds for drug discovery." |
Impact | "Invention Declaration Form has been filed with UCL-B." |
Start Year | 2015 |
Description | Medicinal Chemistry of Autophagy modulators |
Organisation | University College London |
Department | School of Pharmacy |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Testing small molecule compounds generated by the School of Pharmacy in autophagy assays. |
Collaborator Contribution | Generation and provision of 60 compounds for drug discovery. |
Impact | Invention Declaration Form has been filed with UCL-B. Discussions about licensing of compounds with industry partners started. |
Start Year | 2015 |
Description | PROTAC Design for ATG4B |
Organisation | University College London |
Department | School of Pharmacy |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We are developing assays to monitor autophagy in pancreatic tumour cell lines with the aim to use these models to test small molecule compounds as potential therapeutics for pancreatic cancer. |
Collaborator Contribution | The Drug Discovery Group at UCL School of Pharmacy are collaborating in the design and development of PROTAC-based chemicals for treatment of pancreatic cancer. The collaborators perform chemical synthesis of novel compounds for this project. |
Impact | There are no outputs yet. There is potential for drug development and a potential benefit for patients with pancreatic cancer. |
Start Year | 2020 |
Description | PerkinElmer |
Organisation | Perkin Elmer |
Country | United States |
Sector | Private |
PI Contribution | Closely working together on the development of high-content screening technologies. We provide expertise and knowledge. |
Collaborator Contribution | We have received free hardware and software upgrades, e.g. free 5x objective and software upgrades. |
Impact | This has enabled the use of additional technologies on the platform, e.g. Presiscan, FRET. |
Start Year | 2017 |
Description | Prof. Charles Bangham, Imperial College |
Organisation | Imperial College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Discovered new host factor involved in HIV-1 replication that affects integration site selection. |
Collaborator Contribution | High through put sequencing of HIV-1 integration sites. |
Impact | one paper in preparation, one grant application submitted to MRC. |
Start Year | 2012 |
Description | Prof. Christopher Moody and Dr. Russell Kitson, University of Nottingham |
Organisation | University of Nottingham |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Provided data and expertise on the role of Hsp90 in HIV-1 latency. |
Collaborator Contribution | Provided new chemical compounds, inhibitors of Hsp90. |
Impact | one paper in PNAS: Anderson, I., Low, J. S., Weston, S., Weinberger, M., Zhyvoloup, A., Labokha, A. A., Corazza, G., Kitson, R. A., Moody, C. J., Marcello, A., Fassati, A. (2014). Heat shock protein 90 controls HIV-1 reactivation from latency. Proc Natl Acad Sci U S A doi:10.1073/pnas.1320178111. Multidisciplinary: Chemistry, Biology, Medicine |
Start Year | 2012 |
Description | Prof. Hiroyuki Osada |
Organisation | RIKEN |
Country | Japan |
Sector | Public |
PI Contribution | Small molecule screening and drug discovery |
Collaborator Contribution | Provision of small molecule library "NPDepo" |
Impact | n/a |
Start Year | 2011 |
Description | Prof. Olivier Schwartz |
Organisation | Pasteur Institute, Paris |
Country | France |
Sector | Charity/Non Profit |
PI Contribution | Provided data and expertise on the role of Hsp90 in HIV-1 infection. |
Collaborator Contribution | Provided data and expertise on mechanisms contributing to enhanced HIV-1 replication during hyperthermia (fever). |
Impact | One paper in PLoS Pathogens describing the effect of fever on HIV-1 replication and the role of Hsp90. Roesch, F., Meziane, O., Kula, A., Nisole, S., Porrot, F., Anderson, I., Mammano, F., Fassati, A., Marcello, A., Benkirane, M., Schwartz, O. (2012). Hyperthermia Stimulates HIV-1 Replication. PLoS Pathog 8(7), Artn e1002792 doi:10.1371/journal.ppat. Author URL |
Start Year | 2011 |
Description | Prof. Robin A. Weiss and Dr. Laura McCoy |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Performed novel high through put screening to novel broadly HIV-1 cross-neutralising Llama VHHs |
Collaborator Contribution | Provided library from vaccinated Llamas and performed molecular analyses of novel VHHs identified by the screening. |
Impact | Identified three novel broadly cross-neutralising VHHs targeting the CD4-binding site. Determined how such VHHs have emerged following vaccination by deep sequencing. One paper in PLoS Pathogens. McCoy, L.E., Rutten, L., Frampton, D., Anderson, I., Granger, L., Bashford-Rogers, L., Dekkers, G., Strokappe, N.M., Seaman, M.S., Koh, W., Grippo, V., Kliche, A., Verrips, T., Kellam, P., Fassati, A., Weiss, R.A. Molecular evolution of broadly neutralizing llama antibodies to the CD4-binding site of HIV-1. PLoS Pathog. In press.? |
Start Year | 2010 |
Description | RIKEN, Prof. Osada |
Organisation | RIKEN |
Country | Japan |
Sector | Public |
PI Contribution | Small molecule screening and drug discovery |
Collaborator Contribution | Provision of small molecule library "NPDepo" |
Impact | None to date |
Start Year | 2011 |
Description | Samsara Therapeutics |
Organisation | Samsara Therapeutics |
Country | United States |
Sector | Private |
PI Contribution | We are providing expertise in autophagy assays and aging. |
Collaborator Contribution | The partner will provide small molecule chemical libraries and financial contribution. |
Impact | None so far |
Start Year | 2018 |
Description | Small Molecule TIN |
Organisation | University College London |
Department | School of Pharmacy |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | The Small Molecule Therapeutic Innovation Network facilitates exchange of ideas and materials for small molecule drug discovery. Further, this collaboration kickstarts many projects across UCL in the area of early stage drug discovery. |
Collaborator Contribution | Intelectual input, access to instrumentation, access to chemical libraries |
Impact | None so far |
Start Year | 2018 |
Description | Targeting ATG4B in cancer |
Organisation | AstraZeneca |
Country | United Kingdom |
Sector | Private |
PI Contribution | We are working closely together with AstraZeneca to identify small molecule inhibitors of autophagy. We have received a small molecule library from AstraZeneca and will perform the high-throughput screening in our lab. Validation of hits will be performed jointly in a collaboration. |
Collaborator Contribution | Provision of small molecule compounds and expertise/advice. |
Impact | Provision of small molecule compound library and expertise in drug discovery |
Start Year | 2020 |
Description | Testing ATG4B inhibitors in cell-based assays |
Organisation | University of Antwerp |
Country | Belgium |
Sector | Academic/University |
PI Contribution | The partner provides us with small molecule compounds targeting the autophagy protease ATG4B for testing in cell-based assays that we have developed. |
Collaborator Contribution | The partner provides us with small molecule compounds targeting the autophagy protease ATG4B for testing in cell-based assays that we have developed. |
Impact | Research data that will be published eventually. |
Start Year | 2020 |
Company Name | Virology Research Services |
Description | Virology Research Services provides a range of outsourced virology testing and analysis services. |
Year Established | 2018 |
Impact | Screening anti-viral compounds |
Website | http://virologyresearchservices.com |
Description | Academic RNAi Screening Meeting |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | Yes |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | The meetings proved very popular and as places are limited, attendees information is made available to other attendees as part of a delegate pack (or can equally be kept confidential if preferred). In addition, for those who stay overnight there is the opportunity to meet up with other delegates in an ad hoc, informal way either on the evening before or after the meeting. The meetings proved very popular. |
Year(s) Of Engagement Activity | 2011,2012,2014 |
URL | http://hts.cancerresearchuk.org/rnaiMeeting/index.php |
Description | Academic RNAi Screening meeting |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | No |
Type Of Presentation | workshop facilitator |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | 120 Researchers attended a conference co-organized by Mike Howell, Steve Brown, Emma Shanks and myself. There were talks and panel discussions on this one-day meeting. The majority of attendants felt that the conference attracted important scientists in the field and many expressed the notion that this will impact the way they plan to do their research. Industrial partners have expressed satisfaction with the level of engagement with researchers, which will give them leads for commercialisation of their products. |
Year(s) Of Engagement Activity | 2011,2013,2014 |
Description | Autophagy UK Network meeting 2017 |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Postgraduate students |
Results and Impact | 150 researchers, students, representatives from companies and journals came together to discuss the latest advances in the field of autophagy research in Longon. I was one of two organisers for the entire event. |
Year(s) Of Engagement Activity | 2017 |
URL | http://autophagy.uk |
Description | Cellectricon workshop |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | - |
Year(s) Of Engagement Activity | 2012 |
Description | ELA Drug Discovery Automation - HCS and Cell Based Assays conference |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | Yes |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Role: Scientific Advisory Board member and chair |
Year(s) Of Engagement Activity | 2014 |
Description | High-Content Biology Lab Opening Symposium |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Other audiences |
Results and Impact | 120 researchers attended the Opening Symposium for the High-Content Screening facility, which sparked interest in accessing the facility from academics and industry partners. |
Year(s) Of Engagement Activity | 2018 |
Description | Lab Tour for Pancreatic Cancer UK and General Public |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | This event was a Lab Tour, sponsored by Pancreatic Cancer UK, for supporters, patients and carers of patients with Pancreatic Cancer. I have presented my lab/facility in a talk and a lab tour, which sparked a lively discussion with the attendees. |
Year(s) Of Engagement Activity | 2019 |
Description | Open day/Science Fair |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Type Of Presentation | Workshop Facilitator |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | An open day/science fair for MRC funded researchers at UCL - LMCB a principle host and organiser. 500 members of public attended and took part in lectures, demonstrations and other events. Part of MRC Centenary celebrations. Significant feedback from public impressed by presentations and visibility of MRC funded research. |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.ucl.ac.uk/lmcb/lmcb-takes-lead-mrc-centenary-celebrations-ucl |
Description | PCUK Breakfast |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | Around 30 members of the general public attended a Breakfast workshop organised by Pancreatic Cancer UK to learn about new research in the area of pancreatic cancer. I gave a lecture on our new project, which generated a lot of interested from the attendees. |
Year(s) Of Engagement Activity | 2019 |
Description | Royal Reception |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Supporters |
Results and Impact | The charitable organization Action Medical Research invited our research team to present at a Royal Reception at Buckingham Palace. HRH Prince Philip was hosting the event and there were approx 50-60 potential charitable donors present who engaged with our research presentation. The donors were very impressed and as a consequence willing to donate funding towards research into childhood diseases. A lot of the people reported that they learned something new and everyone was engaging in discussions around health, scientific research and patient benefit. |
Year(s) Of Engagement Activity | 2017 |
Description | Royal visit by HRH Princess Anne |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Policymakers/politicians |
Results and Impact | Visit from HRH Princess Anne to the High-Content Biology Screening laboratory, as part of the opening of the UCL-Zeiss Multimodal Imaging Centre. |
Year(s) Of Engagement Activity | 2020 |
Description | SMi 9th Imaging in Cancer Drug Development conference |
Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
Part Of Official Scheme? | No |
Type Of Presentation | keynote/invited speaker |
Geographic Reach | International |
Primary Audience | Other academic audiences (collaborators, peers etc.) |
Results and Impact | Role: chair |
Year(s) Of Engagement Activity | 2013 |
Description | School Visit |
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 | About 20 A-level school children visited the High-Content Biology Laboratory and were given an introduction to lab equipment and work practices. The school reported increased interested in STEM based subjects from their pupils following the visit. |
Year(s) Of Engagement Activity | 2020 |
Description | School Visit (UCL Syddanmark, Denmark) |
Form Of Engagement Activity | Participation in an open day or visit at my research institution |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Schools |
Results and Impact | 14 Students attended a workshop presentation and a tour of the high-throughput screening facility, which led to very fruitful discussion afterwards. The students were looking to explore career track options at that time. Several students indicated that they would now consider a career in science rather than as medical assistant. |
Year(s) Of Engagement Activity | 2014 |
Description | School visit |
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 | Approx 20 school children visited the screening lab and were given hands-on introduction to research in my lab. |
Year(s) Of Engagement Activity | 2019 |
Description | School visit |
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 | School visit with a tour of the MRC funded screening facility and demonstration of experiments |
Year(s) Of Engagement Activity | 2012,2013,2014,2015,2016 |
Description | Scientific Advisory Board Expert Panel for the Dementia Discovery Fund |
Form Of Engagement Activity | A formal working group, expert panel or dialogue |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Industry/Business |
Results and Impact | The Scientific Advisory Board of the Dementia Discovery Fund in collaboration with Alzheimers Research UK, invited me as an expert panel member to discuss the role of Autophagy in Alzheimer's disease. The SAB (composed of leading experts in the pharmaceutical industry and charities) explored the possbility to invest in the development of autophagy modulating drugs for treatment of Alzheimer's disease. This discussion had an immediate impact on funding decisions and the policy of the Dementia Discovery Fund going forward in this area. |
Year(s) Of Engagement Activity | 2019 |