Exploitation of mouse models to validate protein kinases as drug targets
Lead Research Organisation:
MRC Protein Phosphorylation and Ubiquitylation Unit
Department Name: UNLISTED
Abstract
To be supplied at a later date
Technical Summary
The MRC Protein Phosphorylation Unit?s collaboration with the pharmaceutical industry on ?mammalian protein kinases?, which started in 1998, has become a model for how academia and industry should interact. Its benefits to pharma recently led to renewal of support from five major companies for another four years. The spectacular success of Dario Alessi?s team in exploiting gene-targeted mouse lines to validate protein kinases as drug targets was a key factor in renewal. These experiments included a demonstration that mice expressing reduced levels of the protein kinase PDK1 are massively protected against tumourigenesis caused by loss of one allele of PTEN, a gene commonly mutated in cancer. This study led nine companies to licence the Unit?s patents filed by MRC. The first drug to enter clinical trials recently triggered initial milestone payments of #300,000 to MRC. Dario?s team also exploited mice with reduced levels of the protein kinase LKB1 to demonstrate that the anti-diabetic drug metformin, and other activators of the protein kinase AMPK, delayed PTEN-induced tumourigenesis by several months. This proposal requests funding to expand this successful programme beyond the level possible with current support, to validate protein kinases as drug targets for inflammatory diseases, diabetes and a neurodegenerative disease, as well as cancer, and so further enhance the value of our pharmaceutical collaboration.
Organisations
- MRC Protein Phosphorylation and Ubiquitylation Unit (Lead Research Organisation)
- Technical University of Munich (Collaboration)
- Memorial Sloan Kettering Cancer Center (Collaboration)
- Kiel University (Collaboration)
- University of Manitoba (Collaboration)
- National Autonomous University of Mexico (Collaboration)
- Cardiff University (Collaboration)
- Pfizer Ltd (Collaboration)
- University of Hong Kong (Collaboration)
- University of Pittsburgh (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- Medical Research Council (MRC) (Collaboration)
- Redx Pharma Plc (Collaboration)
- Denali Therapeutics (Collaboration)
- Avacta Group (Collaboration)
- UNIVERSITY OF CAMBRIDGE (Collaboration)
- MERCK (Collaboration)
- AstraZeneca (United Kingdom) (Collaboration)
- UNIVERSITY OF OXFORD (Collaboration)
- Tokyo Medical and Dental University (Collaboration)
- Johnson & Johnson (Collaboration)
- Boehringer Ingelheim (Collaboration)
- Yale University (Collaboration)
- UNIVERSITY OF EDINBURGH (Collaboration)
- Ubiquigent (Collaboration)
People |
ORCID iD |
Publications
Schönhuber N
(2014)
A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer.
in Nature medicine
Jayachandran N
(2017)
B-cell-intrinsic function of TAPP adaptors in controlling germinal center responses and autoantibody production in mice.
in European journal of immunology
García-Martínez JM
(2011)
Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice.
in British journal of cancer
Zhang J
(2016)
Functional kinomics establishes a critical node of volume-sensitive cation-Cl- cotransporter regulation in the mammalian brain.
in Scientific reports
Wullschleger S
(2011)
How moderate changes in Akt T-loop phosphorylation impact on tumorigenesis and insulin resistance.
in Disease models & mechanisms
Pearce LR
(2011)
Protor-1 is required for efficient mTORC2-mediated activation of SGK1 in the kidney.
in The Biochemical journal
Wullschleger S
(2011)
Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P2 in regulating insulin sensitivity defined by knock-in analysis.
in The Biochemical journal
Rafiqi FH
(2010)
Role of the WNK-activated SPAK kinase in regulating blood pressure.
in EMBO molecular medicine
Finlay DK
(2010)
Temporal differences in the dependency on phosphoinositide-dependent kinase 1 distinguish the development of invariant Valpha14 NKT cells and conventional T cells.
in Journal of immunology (Baltimore, Md. : 1950)
Bouskila M
(2011)
TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development.
in The Biochemical journal
| Description | Equipment grant |
| Amount | £625,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | Equipment grant |
| Amount | £40,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | Equipment grant |
| Amount | £260,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | Exploiting Ser910/935 phosphorylation and 14-3-3 binding to develop biomarkers for LRRK2 activity |
| Amount | £120,431 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 01/2010 |
| End | 01/2012 |
| Description | J MacDonald Menzies |
| Amount | £177,000 (GBP) |
| Organisation | J Macdonald Menzies Charitable Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | |
| Description | LEAPS Award to identify LRRK2 substrates |
| Amount | $1,500,000 (USD) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 02/2012 |
| End | 01/2015 |
| Description | Lanston Award |
| Amount | £17,582 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 01/2018 |
| End | 12/2019 |
| Description | Project grant |
| Amount | £93,000 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | |
| Description | QQ Renewal |
| Amount | £25,590,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Description | Rapid Innovation Award - Identification of substrates and development of a cell-based assay for LRRK2 |
| Amount | £46,500 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 01/2009 |
| End | 01/2010 |
| Description | Renewal of Division of Signal Transduction Therapy Unit |
| Amount | £7,200,000 (GBP) |
| Organisation | Dundee Signal Transduction Therapy (DSTT) Consortium |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | |
| Description | Renewal of MRC Protein Phosphorylation and Ubiquitylation Core Funding |
| Amount | £24,000,000 (GBP) |
| Funding ID | Purchase Order Number: 4050295594 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2013 |
| End | 03/2018 |
| Description | Renewal of MRC-PPU quinquenial funding |
| Amount | £23,100,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2013 |
| End | 03/2018 |
| Description | Tools Development |
| Amount | £83,244 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 10/2018 |
| End | 09/2020 |
| Description | Tools and Animal Models |
| Amount | £54,902 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 07/2018 |
| End | 12/2019 |
| Description | Understanding LRRK2 2 year project grant to fund postdoc in lab |
| Amount | £130,000 (GBP) |
| Organisation | Michael J Fox Foundation |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 01/2010 |
| End | 01/2012 |
| Description | Wellcome Trust Collaborative Projects (Modulation of renal NaCl transporter via angiotensin II-WNK4-SPAK signalling pathway) |
| Amount | £230,172 (GBP) |
| Funding ID | 091415 |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2010 |
| End | 01/2013 |
| Title | development of SPAK knock-in mice |
| Description | Non-WNK-activatable Spak knock-in mice have reduced blood pressure and therefore suggests that inhibitors of SPAK could be developed to treat blood pressure |
| Type Of Material | Model of mechanisms or symptoms - mammalian in vivo |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | None as yet |
| Description | Aaron M |
| Organisation | University of Manitoba |
| Department | Department of Immunology |
| Country | Canada |
| Sector | Academic/University |
| PI Contribution | Provision of TAPP1 and TAPP2 knock-in mice |
| Collaborator Contribution | Studying impact of TAPP1 and TAPP2 mutations in B cell signalling responses |
| Impact | Jayachandran, N., Landego, I., Hou, S., Alessi, D. R. and Marshall, A. J. (2016). B-cell-intrinsic function of TAPP adaptors in controlling germinal center responses and autoantibody production in mice. Eur J Immunol Landego, I., Jayachandran, N., Wullschleger, S., Zhang, T. T., Gibson, I. W., Miller, A., Alessi, D. R. and Marshall, A. J. (2012). Interaction of TAPP adapter proteins with phosphatidylinositol (3,4)-bisphosphate regulates B-cell activation and autoantibody production. Eur J Immunol 42, pp. 2760-2770 |
| Start Year | 2011 |
| Description | Anastasia H |
| Organisation | Denali Therapeutics |
| Country | United States |
| Sector | Private |
| PI Contribution | Provision of reagents technolgy and advice to better study LRRK2 and Rab protein phosphorylation |
| Collaborator Contribution | Urilising the reagents and support provided by us to aide with LRRK2 drug discovery efforts |
| Impact | . |
| Start Year | 2016 |
| Description | Andy C |
| Organisation | Redx Pharma Plc |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Provision of reagents technolgy and advice to better study SGK biology in cancer |
| Collaborator Contribution | Use of our expertise and technology and reagents to identify improved inhibitors of the SGK protein kinase |
| Impact | . |
| Start Year | 2015 |
| Description | Christian P |
| Organisation | University of Kiel |
| Department | Department of Pharmaceutical Chemistry |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | Undertaking kinase assays to assess effects of novel light sensitive kinase inhibitors |
| Collaborator Contribution | development of novel light sensitive kinase inhibitors |
| Impact | Horbert, R., Pinchuk, B., Davies, P., Alessi, D. and Peifer, C. (2015). Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol 10, pp. 2099-2107 |
| Start Year | 2015 |
| Description | D Saur |
| Organisation | Technical University of Munich |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | advice and reagents and techical support |
| Collaborator Contribution | analysed effect of kinase inhibitors and mutations in various models of human tumours |
| Impact | Schonhuber, N., Seidler, B., Schuck, K., Veltkamp, C., Schachtler, C., Zukowska, M., Eser, S., Feyerabend, T. B., Paul, M. C., Eser, P., Klein, S., Lowy, A. M., Banerjee, R., Yang, F., Lee, C. L., Moding, E. J., Kirsch, D. G., Scheideler, A., Alessi, D. R., Varela, I., Bradley, A., Kind, A., Schnieke, A. E., Rodewald, H. R., Rad, R., Schmid, R. M., Schneider, G. and Saur, D. (2014). A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer. Nat Med 20, pp. 1340-1347 Eser, S., et al including Alessi, D. R. and Saur, D. (2013). Selective Requirement of PI3K/PDK1 Signaling for Kras Oncogene-Driven Pancreatic Cell Plasticity and Cancer. Cancer Cell 23, pp. 406-420 |
| Start Year | 2012 |
| Description | DSTT |
| Organisation | AstraZeneca |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | All the Programme Leaders in the MRC Protein Phosphorylation Unit have participated in a major collaboration with the pharmaceutical industry since 1998, termed The Division of Signal Transduction Therapy. From July 2003 to July 2008, the participating pharmaceutical companies were AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck and Co, Merck-Serono and Pfizer. The collaboration was renewed for a further four years in July 2008 with five of these companies (Merck and Co leaving the consortium at this time). This collaboration was renewed for an unprecedented fourth time in July 2013 for a further four years with six pharmaceutical companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janessen Pharmaceutica), Merck-Serono and Pfizer. Each of the six companies pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. For more information see http://www.ppu.mrc.ac.uk/overview/DSTT.php |
| Collaborator Contribution | Benefits from DSTT collaboration The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. 1. It provides an obvious translational outlet to enable our PIs to exploit their research findings. For example, any PI within the MRC-PPU can rapidly let all six pharmaceutical companies know about any new potential exciting research finding that they have made or any drug target that they have identified or validated. This can lead to major collaborations and stimulate one or more of the pharmaceutical companies to initiate a new drug discovery programme. 2. The research support received from this collaboration is invested in the PPU PIs research programmes and provides additional support to several of our Unit's Scientific service teams including our protein production teams, antibody generation team and cloning team. 3. We obtain key reagents including novel inhibitors, genetically modified cell or mice models from our DSTT pharmaceutical company collaborators. 4. The pharmaceutical companies we collaborate with provide us with important knowledge on the most critical research issues of the day for their drug development programmes. This feedback and industry perspective is extremely useful and helps maximise our overall competitiveness. It ensures that the drug discovery research programmes of the PPU PIs are focussed on addressing the most important questions for better understanding and treating disease. 5. The DSTT collaboration greatly benefits our students and postdocs by providing experience in working with industry via their direct involvement in collaborative experiments with pharmaceutical companies. This provides them with a unique insight into the high quality cutting edge research that is taking place within pharmaceutical companies and gives them an awareness of potential careers in industry. This is particularly important given that one of our main priorities is to train tomorrow's industrial researchers and ensure that the future workforce has the high quality scientific and research support skills that the UK economy will be dependent on. |
| Impact | During the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Description | DSTT |
| Organisation | Boehringer Ingelheim |
| Country | Germany |
| Sector | Private |
| PI Contribution | All the Programme Leaders in the MRC Protein Phosphorylation Unit have participated in a major collaboration with the pharmaceutical industry since 1998, termed The Division of Signal Transduction Therapy. From July 2003 to July 2008, the participating pharmaceutical companies were AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck and Co, Merck-Serono and Pfizer. The collaboration was renewed for a further four years in July 2008 with five of these companies (Merck and Co leaving the consortium at this time). This collaboration was renewed for an unprecedented fourth time in July 2013 for a further four years with six pharmaceutical companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janessen Pharmaceutica), Merck-Serono and Pfizer. Each of the six companies pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. For more information see http://www.ppu.mrc.ac.uk/overview/DSTT.php |
| Collaborator Contribution | Benefits from DSTT collaboration The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. 1. It provides an obvious translational outlet to enable our PIs to exploit their research findings. For example, any PI within the MRC-PPU can rapidly let all six pharmaceutical companies know about any new potential exciting research finding that they have made or any drug target that they have identified or validated. This can lead to major collaborations and stimulate one or more of the pharmaceutical companies to initiate a new drug discovery programme. 2. The research support received from this collaboration is invested in the PPU PIs research programmes and provides additional support to several of our Unit's Scientific service teams including our protein production teams, antibody generation team and cloning team. 3. We obtain key reagents including novel inhibitors, genetically modified cell or mice models from our DSTT pharmaceutical company collaborators. 4. The pharmaceutical companies we collaborate with provide us with important knowledge on the most critical research issues of the day for their drug development programmes. This feedback and industry perspective is extremely useful and helps maximise our overall competitiveness. It ensures that the drug discovery research programmes of the PPU PIs are focussed on addressing the most important questions for better understanding and treating disease. 5. The DSTT collaboration greatly benefits our students and postdocs by providing experience in working with industry via their direct involvement in collaborative experiments with pharmaceutical companies. This provides them with a unique insight into the high quality cutting edge research that is taking place within pharmaceutical companies and gives them an awareness of potential careers in industry. This is particularly important given that one of our main priorities is to train tomorrow's industrial researchers and ensure that the future workforce has the high quality scientific and research support skills that the UK economy will be dependent on. |
| Impact | During the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Description | DSTT |
| Organisation | GlaxoSmithKline (GSK) |
| Country | Global |
| Sector | Private |
| PI Contribution | All the Programme Leaders in the MRC Protein Phosphorylation Unit have participated in a major collaboration with the pharmaceutical industry since 1998, termed The Division of Signal Transduction Therapy. From July 2003 to July 2008, the participating pharmaceutical companies were AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck and Co, Merck-Serono and Pfizer. The collaboration was renewed for a further four years in July 2008 with five of these companies (Merck and Co leaving the consortium at this time). This collaboration was renewed for an unprecedented fourth time in July 2013 for a further four years with six pharmaceutical companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janessen Pharmaceutica), Merck-Serono and Pfizer. Each of the six companies pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. For more information see http://www.ppu.mrc.ac.uk/overview/DSTT.php |
| Collaborator Contribution | Benefits from DSTT collaboration The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. 1. It provides an obvious translational outlet to enable our PIs to exploit their research findings. For example, any PI within the MRC-PPU can rapidly let all six pharmaceutical companies know about any new potential exciting research finding that they have made or any drug target that they have identified or validated. This can lead to major collaborations and stimulate one or more of the pharmaceutical companies to initiate a new drug discovery programme. 2. The research support received from this collaboration is invested in the PPU PIs research programmes and provides additional support to several of our Unit's Scientific service teams including our protein production teams, antibody generation team and cloning team. 3. We obtain key reagents including novel inhibitors, genetically modified cell or mice models from our DSTT pharmaceutical company collaborators. 4. The pharmaceutical companies we collaborate with provide us with important knowledge on the most critical research issues of the day for their drug development programmes. This feedback and industry perspective is extremely useful and helps maximise our overall competitiveness. It ensures that the drug discovery research programmes of the PPU PIs are focussed on addressing the most important questions for better understanding and treating disease. 5. The DSTT collaboration greatly benefits our students and postdocs by providing experience in working with industry via their direct involvement in collaborative experiments with pharmaceutical companies. This provides them with a unique insight into the high quality cutting edge research that is taking place within pharmaceutical companies and gives them an awareness of potential careers in industry. This is particularly important given that one of our main priorities is to train tomorrow's industrial researchers and ensure that the future workforce has the high quality scientific and research support skills that the UK economy will be dependent on. |
| Impact | During the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Description | DSTT |
| Organisation | Johnson & Johnson |
| Department | Janssen Pharmaceutica |
| Country | Global |
| Sector | Private |
| PI Contribution | All the Programme Leaders in the MRC Protein Phosphorylation Unit have participated in a major collaboration with the pharmaceutical industry since 1998, termed The Division of Signal Transduction Therapy. From July 2003 to July 2008, the participating pharmaceutical companies were AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck and Co, Merck-Serono and Pfizer. The collaboration was renewed for a further four years in July 2008 with five of these companies (Merck and Co leaving the consortium at this time). This collaboration was renewed for an unprecedented fourth time in July 2013 for a further four years with six pharmaceutical companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janessen Pharmaceutica), Merck-Serono and Pfizer. Each of the six companies pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. For more information see http://www.ppu.mrc.ac.uk/overview/DSTT.php |
| Collaborator Contribution | Benefits from DSTT collaboration The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. 1. It provides an obvious translational outlet to enable our PIs to exploit their research findings. For example, any PI within the MRC-PPU can rapidly let all six pharmaceutical companies know about any new potential exciting research finding that they have made or any drug target that they have identified or validated. This can lead to major collaborations and stimulate one or more of the pharmaceutical companies to initiate a new drug discovery programme. 2. The research support received from this collaboration is invested in the PPU PIs research programmes and provides additional support to several of our Unit's Scientific service teams including our protein production teams, antibody generation team and cloning team. 3. We obtain key reagents including novel inhibitors, genetically modified cell or mice models from our DSTT pharmaceutical company collaborators. 4. The pharmaceutical companies we collaborate with provide us with important knowledge on the most critical research issues of the day for their drug development programmes. This feedback and industry perspective is extremely useful and helps maximise our overall competitiveness. It ensures that the drug discovery research programmes of the PPU PIs are focussed on addressing the most important questions for better understanding and treating disease. 5. The DSTT collaboration greatly benefits our students and postdocs by providing experience in working with industry via their direct involvement in collaborative experiments with pharmaceutical companies. This provides them with a unique insight into the high quality cutting edge research that is taking place within pharmaceutical companies and gives them an awareness of potential careers in industry. This is particularly important given that one of our main priorities is to train tomorrow's industrial researchers and ensure that the future workforce has the high quality scientific and research support skills that the UK economy will be dependent on. |
| Impact | During the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Description | DSTT |
| Organisation | Merck |
| Department | Merck Serono |
| Country | Germany |
| Sector | Private |
| PI Contribution | All the Programme Leaders in the MRC Protein Phosphorylation Unit have participated in a major collaboration with the pharmaceutical industry since 1998, termed The Division of Signal Transduction Therapy. From July 2003 to July 2008, the participating pharmaceutical companies were AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck and Co, Merck-Serono and Pfizer. The collaboration was renewed for a further four years in July 2008 with five of these companies (Merck and Co leaving the consortium at this time). This collaboration was renewed for an unprecedented fourth time in July 2013 for a further four years with six pharmaceutical companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janessen Pharmaceutica), Merck-Serono and Pfizer. Each of the six companies pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. For more information see http://www.ppu.mrc.ac.uk/overview/DSTT.php |
| Collaborator Contribution | Benefits from DSTT collaboration The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. 1. It provides an obvious translational outlet to enable our PIs to exploit their research findings. For example, any PI within the MRC-PPU can rapidly let all six pharmaceutical companies know about any new potential exciting research finding that they have made or any drug target that they have identified or validated. This can lead to major collaborations and stimulate one or more of the pharmaceutical companies to initiate a new drug discovery programme. 2. The research support received from this collaboration is invested in the PPU PIs research programmes and provides additional support to several of our Unit's Scientific service teams including our protein production teams, antibody generation team and cloning team. 3. We obtain key reagents including novel inhibitors, genetically modified cell or mice models from our DSTT pharmaceutical company collaborators. 4. The pharmaceutical companies we collaborate with provide us with important knowledge on the most critical research issues of the day for their drug development programmes. This feedback and industry perspective is extremely useful and helps maximise our overall competitiveness. It ensures that the drug discovery research programmes of the PPU PIs are focussed on addressing the most important questions for better understanding and treating disease. 5. The DSTT collaboration greatly benefits our students and postdocs by providing experience in working with industry via their direct involvement in collaborative experiments with pharmaceutical companies. This provides them with a unique insight into the high quality cutting edge research that is taking place within pharmaceutical companies and gives them an awareness of potential careers in industry. This is particularly important given that one of our main priorities is to train tomorrow's industrial researchers and ensure that the future workforce has the high quality scientific and research support skills that the UK economy will be dependent on. |
| Impact | During the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Description | DSTT |
| Organisation | Pfizer Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | All the Programme Leaders in the MRC Protein Phosphorylation Unit have participated in a major collaboration with the pharmaceutical industry since 1998, termed The Division of Signal Transduction Therapy. From July 2003 to July 2008, the participating pharmaceutical companies were AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Merck and Co, Merck-Serono and Pfizer. The collaboration was renewed for a further four years in July 2008 with five of these companies (Merck and Co leaving the consortium at this time). This collaboration was renewed for an unprecedented fourth time in July 2013 for a further four years with six pharmaceutical companies (AstraZeneca, Boehringer-Ingelheim, GlaxoSmithKline, Janessen Pharmaceutica), Merck-Serono and Pfizer. Each of the six companies pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. For more information see http://www.ppu.mrc.ac.uk/overview/DSTT.php |
| Collaborator Contribution | Benefits from DSTT collaboration The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. 1. It provides an obvious translational outlet to enable our PIs to exploit their research findings. For example, any PI within the MRC-PPU can rapidly let all six pharmaceutical companies know about any new potential exciting research finding that they have made or any drug target that they have identified or validated. This can lead to major collaborations and stimulate one or more of the pharmaceutical companies to initiate a new drug discovery programme. 2. The research support received from this collaboration is invested in the PPU PIs research programmes and provides additional support to several of our Unit's Scientific service teams including our protein production teams, antibody generation team and cloning team. 3. We obtain key reagents including novel inhibitors, genetically modified cell or mice models from our DSTT pharmaceutical company collaborators. 4. The pharmaceutical companies we collaborate with provide us with important knowledge on the most critical research issues of the day for their drug development programmes. This feedback and industry perspective is extremely useful and helps maximise our overall competitiveness. It ensures that the drug discovery research programmes of the PPU PIs are focussed on addressing the most important questions for better understanding and treating disease. 5. The DSTT collaboration greatly benefits our students and postdocs by providing experience in working with industry via their direct involvement in collaborative experiments with pharmaceutical companies. This provides them with a unique insight into the high quality cutting edge research that is taking place within pharmaceutical companies and gives them an awareness of potential careers in industry. This is particularly important given that one of our main priorities is to train tomorrow's industrial researchers and ensure that the future workforce has the high quality scientific and research support skills that the UK economy will be dependent on. |
| Impact | During the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Description | DSTT renewal 2016 |
| Organisation | Boehringer Ingelheim |
| Country | Germany |
| Sector | Private |
| PI Contribution | Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono - each company pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. |
| Collaborator Contribution | The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. |
| Impact | uring the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Start Year | 2016 |
| Description | DSTT renewal 2016 |
| Organisation | GlaxoSmithKline (GSK) |
| Country | Global |
| Sector | Private |
| PI Contribution | Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono - each company pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. |
| Collaborator Contribution | The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. |
| Impact | uring the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Start Year | 2016 |
| Description | DSTT renewal 2016 |
| Organisation | Merck |
| Department | Merck Serono Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Boehringer-Ingelheim, GlaxoSmithKline and Merck-Serono - each company pays £600000 per annum over the four year period. The aim of the collaboration is to help the pharmaceutical companies accelerate the development of drugs that inhibit protein and lipid kinases and phosphatases with therapeutic potential for the treatment of disease. |
| Collaborator Contribution | The MRC-PPU benefits in many ways as a result of the DSTT research collaboration. |
| Impact | uring the collaboration, the Unit has helped to launch and/or accelerate many drug discovery programmes, some of which have entered human clinical trials. The collaboration led the Unit to develop the technology of protein kinase profiling which has developed into an industry worth over £100 million per annum. It also led to the creation of the European Division of Upstate Incorporated in Dundee which currently employs about 50 people. The Unit's first publication on protein kinase profiling was named in 2009 by the Institute for Scientific Information, Philadelphia as Europe's most cited paper in the field of Cel Biology from 1996-2007, with over 2,200 citations. During the collaboration, the Unit has filed 36 patents and 30 licenses have been taken up by the pharmaceutical industry. The DSTT is widely regarded as a model of how academia and industry should interact for which it received a Queen's Anniversary Award for Higher Education which was presented by the Queen and Duke of Edinburgh at Buckingham Palace in February 2006. GlaxoSmithKline have announced that their BRAF protein kinase inhibitor Dabrafenib (Tafinlar), has been approved by both the European Commission and the United States Food and Drug Administration for the treatment of unresectable or metastatic melanoma associated with the BRAF V600E mutation. Unresectable melanoma is that which cannot be removed by surgery, while metastatic melanoma is that which has spread to other parts of the body. The new drug was developed employing BRAF enzymes generated by researchers in the Division of Signal Transduction Therapy (DSTT) in the College of Life Sciences at Dundee. |
| Start Year | 2016 |
| Description | Gerardo G |
| Organisation | National Autonomous University of Mexico |
| Country | Mexico |
| Sector | Academic/University |
| PI Contribution | Undertaking biochemical analysis of WNK signalling pathways as well as provision of advice, reagents and technology |
| Collaborator Contribution | Performing physiological measuremnts of WNK signalling pathway in mice |
| Impact | Melo, Z., de los Heros, P., Cruz-Rangel, S., Vazquez, N., Bobadilla, N. A., Pasantes-Morales, H., Alessi, D. R., Mercado, A. and Gamba, G. (2013). N-terminal serine dephosphorylation is required for KCC3 cotransporter full activation by cell swelling. J Biol Chem 288, pp. 31468-31476 Castaneda-Bueno, M., Cervantes-Perez, L. G., Vazquez, N., Uribe, N., Kantesaria, S., Morla, L., Bobadilla, N. A., Doucet, A., Alessi, D. R. and Gamba, G. (2012). Activation of the renal Na+:Cl- cotransporter by angiotensin II is a WNK4-dependent process. Proc Natl Acad Sci U S A 109, pp. 7929-7934 Rafiqi, F. H., Zuber, A. M., Glover, M., Richardson, C., Fleming, S., Jovanovic, S., Jovanovic, A., O'Shaughnessy, K. M. and Alessi, D. R. (2010). Role of the WNK-activated SPAK kinase in regulating blood pressure. EMBO Mol Med 2, pp. 63-75 San-Cristobal, P., Pacheco-Alvarez, D., Richardson, C., Ring, A. M., Vazquez, N., Rafiqi, F. H., Chari, D., Kahle, K. T., Leng, Q., Bobadilla, N. A., Hebert, S. C., Alessi, D. R., Lifton, R. P. and Gamba, G. (2009). Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway. Proc Natl Acad Sci U S A 106, pp. 4384-9 |
| Start Year | 2008 |
| Description | J Baselga |
| Organisation | Memorial Sloan Kettering Cancer Center |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Undertaking functional studies on the SGK1 and SGK3 protein kinases in the field of cancer research |
| Collaborator Contribution | Undertaking xenograph analysis of effects of Akt and SGK inhibitors on tumour development |
| Impact | Bago, R., Sommer, E., Castel, P., Crafter, C., Bailey, F. P., Shpiro, N., Baselga, J., Cross, D., Eyers, P. A. and Alessi, D. R. (2016). The hVps34-SGK3 pathway alleviates sustained PI3K/Akt inhibition by stimulating mTORC1 and tumour growth. EMBO J 35, pp. 1902-1922 Castel, P., Ellis, H., Bago, R., Toska, E., Razavi, P., Carmona, F. J., Kannan, S., Verma, C. S., Dickler, M., Chandarlapaty, S., Brogi, E., Alessi, D. R., Baselga, J. and Scaltriti, M. (2016). PDK1-SGK1 Signaling Sustains AKT-Independent mTORC1 Activation and Confers Resistance to PI3Kalpha Inhibition. Cancer Cell 30, pp. 229-242 |
| Start Year | 2015 |
| Description | Jason B |
| Organisation | Ubiquigent |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Provision of reagents technolgy and advice to help ubiquigent provide services and reagents to its customers |
| Collaborator Contribution | Ubiqigent sells our reagents to customers and also uses our advice reagents and expertise to help provide its customers with improved services |
| Impact | . |
| Start Year | 2010 |
| Description | Jon E |
| Organisation | University of Oxford |
| Department | Wellcome Trust Centre for Human Genetics |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | Undertaking mutational analysis to help study crystal structures of the SGK3 protein kinase |
| Collaborator Contribution | Crystallisation of the SGK3 protein kinase |
| Impact | . |
| Start Year | 2015 |
| Description | Kevin O |
| Organisation | University of Cambridge |
| Department | Department of Anglo-Saxon, Norse and Celtic |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | provided genetically modified mice, reagents, technology and advice |
| Collaborator Contribution | Undertook blood pressure measuremnts in mice and other physiological experiments |
| Impact | Zhang, J., Siew, K., Macartney, T., O'Shaughnessy, K. M. and Alessi, D. R. (2015). Critical role of the SPAK protein kinase CCT domain in controlling blood pressure. Hum Mol Genet 24, pp. 4545-4558 Rafiqi, F. H., Zuber, A. M., Glover, M., Richardson, C., Fleming, S., Jovanovic, S., Jovanovic, A., O'Shaughnessy, K. M. and Alessi, D. R. (2010). Role of the WNK-activated SPAK kinase in regulating blood pressure. EMBO Mol Med 2, pp. 63-75 |
| Start Year | 2009 |
| Description | Kris K |
| Organisation | Yale University |
| Department | School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Undertaking biochemical analysis of WNK signalling pathways as well as provision of advice, reagents and technology |
| Collaborator Contribution | Performing physiological measuremnts of WNK signalling pathway in mice |
| Impact | Zhang, J., Gao, G., Begum, G., Wang, J., Khanna, A. R., Shmukler, B. E., Daubner, G. M., de Los Heros, P., Davies, P., Varghese, J., Bhuiyan, M. I., Duan, J., Zhang, J., Duran, D., Alper, S. L., Sun, D., Elledge, S. J., Alessi, D. R. and Kahle, K. T. (2016). Functional kinomics establishes a critical node of volume-sensitive cation-Cl- cotransporter regulation in the mammalian brain. Sci Rep 6, pp. 35986 Alessi, D. R., Zhang, J., Khanna, A., Hochdorfer, T., Shang, Y. and Kahle, K. T. (2014). The WNK-SPAK/OSR1 pathway: Master regulator of cation-chloride cotransporters. Sci Signal 7, pp. re3 de Los Heros, P., Alessi, D. R., Gourlay, R., Campbell, D. G., Deak, M., Macartney, T. J., Kahle, K. T. and Zhang, J. (2014). The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+-Cl- co-transporters. Biochem J 458, pp. 559-573 San-Cristobal, P., Pacheco-Alvarez, D., Richardson, C., Ring, A. M., Vazquez, N., Rafiqi, F. H., Chari, D., Kahle, K. T., Leng, Q., Bobadilla, N. A., Hebert, S. C., Alessi, D. R., Lifton, R. P. and Gamba, G. (2009). Angiotensin II signaling increases activity of the renal Na-Cl cotransporter through a WNK4-SPAK-dependent pathway. Proc Natl Acad Sci U S A 106, pp. 4384-9 |
| Start Year | 2011 |
| Description | MRC HGU |
| Organisation | Medical Research Council (MRC) |
| Department | MRC Human Genetics Unit |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | advice and reagents and techical support |
| Collaborator Contribution | They undertook the bulk of the experimentation |
| Impact | . |
| Start Year | 2010 |
| Description | Mike C |
| Organisation | University of Edinburgh |
| Department | MRC Centre for Inflammation Research |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Undertook key experiments on TTBK2 kinase and advice and reagents and techical support |
| Collaborator Contribution | Undertook detailed synapse function studies and generation of primary neurons |
| Impact | Zhang, N., Gordon, S. L., Fritsch, M. J., Esoof, N., Campbell, D. G., Gourlay, R., Velupillai, S., Macartney, T., Peggie, M., van Aalten, D. M., Cousin, M. A. and Alessi, D. R. (2015). Phosphorylation of Synaptic Vesicle Protein 2A at Thr84 by Casein Kinase 1 Family Kinases Controls the Specific Retrieval of Synaptotagmin-1. J Neurosci 35, pp. 2492-2507 |
| Start Year | 2013 |
| Description | Neil B |
| Organisation | University of Oxford |
| Department | Nuffield Department of Medicine |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Undertaking mutational analysis to help study crystal structures of the WNK protein kinase |
| Collaborator Contribution | Crystallisation of the WNK protein kinase |
| Impact | Schumacher, F. R., Sorrell, F. J., Alessi, D. R., Bullock, A. N. and Kurz, T. (2014). Structural and biochemical characterization of the KLHL3-WNK kinase interaction important in blood pressure regulation. Biochem J 460, pp. 237-246 |
| Start Year | 2013 |
| Description | Paul K F |
| Organisation | Avacta Group |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Provision of reagents technolgy and advice to generate new affimers to better study protein phosphorylation |
| Collaborator Contribution | Use of our expertise and technology and reagents to develop novel affimers |
| Impact | . |
| Start Year | 2016 |
| Description | Role of LRRK2[R1441G] mutations in Parkinson's |
| Organisation | University of Hong Kong |
| Department | Li Ka Shing School of Medicine |
| Country | Hong Kong |
| Sector | Academic/University |
| PI Contribution | The group of Prof Ho have generated an LRRK2[R1441G] knock-in mouse that mimics one of the major disease causing mutations in human Parkinson's patients. We have initiated a major collaboration to discover how this mutation induces phosphorylation of Rab isoforms by LRRK2 and work out how this is linked to development of Parkinson's disease. |
| Collaborator Contribution | Providing LRRK2[R1441G] knock-in mouse and helping with some of the experiments |
| Impact | none as yet-but we should have some interesting data that should be published in 2016 |
| Start Year | 2015 |
| Description | Shinichi U |
| Organisation | Tokyo Medical and Dental University |
| Department | Department of Neurology and Neurological Science |
| Country | Japan |
| Sector | Academic/University |
| PI Contribution | Undertaking biochemical analysis of WNK signalling pathways as well as provision of advice, reagents and technology |
| Collaborator Contribution | Performing physiological measuremnts of WNK signalling pathway in mice |
| Impact | Nishida, H., Sohara, E., Nomura, N., Chiga, M., Alessi, D. R., Rai, T., Sasaki, S. and Uchida, S. (2012). Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Activates the WNK-OSR1/SPAK-NCC Phosphorylation Cascade in Hyperinsulinemic db/db Mice. Hypertension 60, pp. 981-990 Oi, K., Sohara, E., Rai, T., Misawa, M., Chiga, M., Alessi, D. R., Sasaki, S. and Uchida, S. (2012). A minor role of WNK3 in regulating phosphorylation of renal NKCC2 and NCC co-transporters in vivo. Biol Open 1, pp. 120-127 Susa, K., Kita, S., Iwamoto, T., Yang, S. S., Lin, S. H., Ohta, A., Sohara, E., Rai, T., Sasaki, S., Alessi, D. R. and Uchida, S. (2012). Effect of heterozygous deletion of WNK1 on the WNK-OSR1/ SPAK-NCC/NKCC1/NKCC2 signal cascade in the kidney and blood vessels. Clin Exp Nephrol 16, pp. 530-538 Chiga, M., Rafiqi, F. H., Alessi, D. R., Sohara, E., Ohta, A., Rai, T., Sasaki, S. and Uchida, S. (2011). Phenotypes of pseudohypoaldosteronism type II caused by the WNK4 D561A missense mutation are dependent on the WNK-OSR1/SPAK kinase cascade. J Cell Sci 124, pp. 1391-1395 |
| Start Year | 2011 |
| Description | Timothy G |
| Organisation | University of Pittsburgh |
| Department | Pittsburgh Institute for Neurodegenerative Diseases |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | Provisions of Regeants, technology and experimental support to measure the impact that rotenone has on LRRK2 protein kinase activity |
| Collaborator Contribution | Undertaking assays to measure LRRK2 and Rab phosphorylation using reagents provided by us |
| Impact | , |
| Start Year | 2016 |
| Description | Youcef M |
| Organisation | Cardiff University |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Undertaking assays to study inhibitors of the WNK signalling pathway as well as advice, reagents and technology |
| Collaborator Contribution | Generation of novel kinase inhibitors that tartget components of the WNK signalling pathway |
| Impact | . |
| Start Year | 2015 |
| Description | Attendance at the Scottish Parliament - MRC |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Myself, Professor John Rouse and Dr Paul Davies attended an event in the Scottish Parliament on 6th February to support the Medical Research Council's investment in science in Scotland and to present the work that we are doing in the MRC-PPU to MSPs. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Connect and collaborate Parkinson's outreach event in the School of Life Sciences |
| 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 | Patients, carers and/or patient groups |
| Results and Impact | On November 7 of this year, the chief executive team of Parkinson's UK including CEO Caroline Rassell, Deputy director of research Professor David Dexter and the new Scotland director James Jopling visited the Parkinson's research team at the University of Dundee. In the morning, researchers from Dundee including Professor Dario Alessi, Dr. Paul Davies, ProfessorMiratul Muqit, Dr. Andy Howden, Professor Ian Ganley and Dr. Esther Sammler, from Aberdeen Professor Bettina Platt and Julie Jones, from St. Andrews Doris Chen and from Edinburgh, Professor Tilo Kunath gave an overview of their work. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Dolly scientist backs research drive to tackle Parkinson's disease - University of Dundee Press release |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other audiences |
| Results and Impact | Professor Sir Ian Wilmut - who led the team that created Dolly the sheep - has backed an initiative to tackle Parkinson's disease, after being diagnosed with the condition. The eminent scientist announced his diagnosis today - World Parkinson's Day - ahead of the launch of a major research programme that will see experts at the Universities of Edinburgh and Dundee join forces in the quest to better understand the disease. They will set up infrastructure to enable the first trials in Scotland in a generation for therapies that aim to slow down Parkinson's disease progression. The new Dundee-Edinburgh Parkinson's Research Initiative aims to probe the causes of disease and translate scientific discoveries into new therapies. The ultimate goal is to find new approaches to predict and prevent Parkinson's, and to facilitate clinical testing of therapies aimed at slowing or reversing disease progression. Professor Dario Alessi, of the University of Dundee, said, "All attempts to slow the progression of Parkinson's have thus far failed. Surprisingly today's most widely utilised Parkinson's drug levodopa was first used in the clinic in 1967. "In recent years, our knowledge of the genetics and biology underlining Parkinson's disease has exploded. I feel optimistic and it is not unrealistic that with a coordinated research effort, major strides towards better treating Parkinson's disease can be made." Parkinson's disease is a progressive condition caused by damage to specific cells in the brain. It affects movement and is often associated with involuntary shaking. Therapies that reduce symptoms can help to prolong quality of life, but currently there are no treatments to slow or halt the progression of the disease. At present, Scottish patients seeking to take part in clinical trials of treatments that could delay disease progression are required to travel to centres in England or Wales, or even abroad. Professor Wilmut said, "Initiatives of this kind are very effective not only because they bring more people together, but because they will include people with different experience and expertise. It was from such a rich seedbed that Dolly developed and we can hope for similar benefits in this project." Dolly the sheep was created at The Roslin Institute in 1996 by a multidisciplinary research team led by Professor Wilmut. She was the first clone of an animal from an adult cell and her birth turned scientific thinking on its head. It showed that cells from anywhere in the body could be made to behave like a newly fertilised egg - something that scientists had thought was impossible. This breakthrough paved the way for others to develop a method of using adult cells to produce reprogrammable cells that could develop into any kind of tissue in the body - so called induced pluripotent stem cells, or iPSCs. These cells hold great promise as therapies because of their potential to repair damaged tissues. The first clinical trials of iPSCs for Parkinson's disease are to begin in Japan later this year. Dr Tilo Kunath, of Edinburgh's Medical Research Council Centre for Regenerative Medicine, said, "People with Parkinson's urgently require access to earlier and more accurate diagnosis, better prediction of how their disease will progress, and most importantly, the opportunity to participate in clinical trials of new treatments. This new research partnership aims to make these hopes a reality for people in Scotland." There are more than 12,000 people living with Parkinson's disease in Scotland. Across the UK, the number is expect to double in the next 50 years as the population grows and people live longer. The Dundee-Edinburgh Parkinson's Research Initiative will be formally launched at a public event at the Royal College of Physicians of Edinburgh on Friday 13 April. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Edinburgh Parkinson's seminar that was delivered by Giovanni Mallucci |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | PRC PPU Unit co-sponsored the Edinburgh Parkinson's seminar that was delivered by Giovanni Mallucci in which 300 patients and family members attended. Professor Dario Alessi gave the vote of thanks at the end of the seminar. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Forthill Primary School Visit - June, 2014 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | Scientists and support staff from the MRC PPU recently enjoyed a visit with a P3 class at Forthill Primary for a fun morning of hands on experiments. Overall, the morning proved to be a big hit and provided a fun introduction to hands-on general science experiments for the P3 children. There was plenty of loud vocal appreciation from the children and assurances from many that scientist is now their primary career choice. |
| Year(s) Of Engagement Activity | 2014 |
| Description | Interview to discuss LRRK2 and Parkinson's Disease |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Interview with "Tomorrow Edition" to discuss Parkinson's disease and LRRK2. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://tmrwedition.com/2018/09/18/interview-with-biochemist-and-lrrk2-expert-prof-dario-alessi/ |
| Description | Interview with Journalist from Bloomberg News |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | On Thursday 19th January, I spent ~90 minutes talking with Robert Langreth, a Journalist from Bloomberg News, on the subject of Pakrinson disease, Alzheimer's and other neurological diseases. Robert was looking to write a story on where the efforts for parkinson's disease modifying drugs stand. Robert was interested in finding out more about lrrk2 and parkinson's disease research. Robert advised he had also spoken with the MJFF and ASAP re how the influx of funding from MJFF/Sergey Brin/Asap is changing things, and how is the approach taken in parkinson's differ from the more single minded focus in Alzheimer's. |
| Year(s) Of Engagement Activity | 2023 |
| Description | MRC-PPU Collaboration with Baldragon Academy 2014 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The Medical Research Council's Protein Phosphorylation Ubiquitylation Unit (MRCPPU), part of The University of Dundee, has prioritized public engagement in an effort to engage the general public and ensure that the research activities and breakthroughs are communicated to the community. Of equal importance in these communication efforts is educational outreach to students within the Dundee community. Thus, during session 2014 -2015 and 2015-2016 school year, the MRC-PPU will partner with a local secondary school -- Baldragon Academy (BA). Teachers in BA's Science Department will collaborate with scientists at the MRC-PPU in an educational outreach effort (see Appendix 1). The purpose of this project is to increase interest and engagement in science and related careers. It will be starting in August 2014 with the S1 pupils. Scientists from the unit will be working with the pupils on a monthly basis at the school during their science classes and will be providing them with opportunities to take part in various science experiments and demonstrations (aligned with Scotland's Curriculum for Excellence). The scientists are leaders in their field of research and as such come from all over the world. They are currently based in Dundee." Thus far, student have been very enthusiastic about the labs and very receptive to the volunteers. They have asked a multitude of quesitons and have even asked volunteers back to visit. |
| Year(s) Of Engagement Activity | 2014 |
| Description | MRC-PPU Collaboration with Baldragon Academy 2015 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Schools |
| Results and Impact | The Medical Research Council's Protein Phosphorylation Ubiquitylation Unit (MRCPPU), part of The University of Dundee, has prioritized public engagement in an effort to engage the general public and ensure that the research activities and breakthroughs are communicated to the community. Of equal importance in these communication efforts is educational outreach to students within the Dundee community. Thus, during session 2014 -2015 and 2015-2016 school year, the MRC-PPU will partner with a local secondary school -- Baldragon Academy (BA). Teachers in BA's Science Department will collaborate with scientists at the MRC-PPU in an educational outreach effort (see Appendix 1). The purpose of this project is to increase interest and engagement in science and related careers. It will be starting in August 2014 with the S1 pupils. Scientists from the unit will be working with the pupils on a monthly basis at the school during their science classes and will be providing them with opportunities to take part in various science experiments and demonstrations (aligned with Scotland's Curriculum for Excellence). The scientists are leaders in their field of research and as such come from all over the world. They are currently based in Dundee. Thus far, student have been very enthusiastic about the labs and very receptive to the volunteers. They have asked a multitude of questions and have even asked volunteers back to visit. We have also had numerous students of different ages from the school ask to participate in work experience activities to learn more about the Unit and science in general. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Meeting with UoD alumni |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Other audiences |
| Results and Impact | Myself, and other members of SLS, participated in an event which welcomed medics who graduated from Dundee University in 1977. I discussed with them the current research that is taking place in our Unit and beyond in Dundee. |
| Year(s) Of Engagement Activity | 2022 |
| Description | Parkinson's Patient/Parkinson's Uk organised event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Professional Practitioners |
| Results and Impact | Gave a talk on LRRK2 in Parkinson's at a Parkinson's Patient/Parkinson's Uk organised event. |
| Year(s) Of Engagement Activity | 2018 |
| Description | Parkinson's UK Supporters Event |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Discussing mine and the units research and projects to Parkinson's supporters at the Parkinson's UK Supporters Event on 2nd July 2018 |
| Year(s) Of Engagement Activity | 2018 |
| Description | Patient visit and generous donation by Kiltwalk fundraiser Moira Cardosi towards Parkinson's disease research |
| 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 | Patients, carers and/or patient groups |
| Results and Impact | Moira Cardosi, Barbara Lynch and Liz Haughey visited the MRC Protein Phosphorylation Unit to meet with myself and other members of the team to hear about our exciting research into Parkinson's disease. They also presented us with a cheque in excess of £3,000 - funds that Moira Cardosi had raised during the 2019 Kiltwalk in memory of Mrs Lynch's late husband who had suffered from the condition. During a tour of the MRC PPU laboratory our visitors also gained a first-hand impression of our work and why we believe that better understanding the causes of Parkinson's disease will eventually lead to finding a cure. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.ppu.mrc.ac.uk/news/generous-donation-kiltwalk-fundraiser-moira-cardosi-towards-parkinson... |
| Description | Pioneer of Digital Blood Glucose Meter Technology visits MRC-PPU |
| 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 | Professional Practitioners |
| Results and Impact | Professor Ian Shanks FRS and his daughter Dr Emma Shanks visited the MRC Protein Phosphorylation and Ubiquitylation Unit (PPU) on January 23rd to hear about the research being undertaken at the PPU. Ian Shanks is a pioneer of liquid crystal display (LCD) and adapted this to develop the first digital blood glucose sensor in the 1980s which has transformed the management of diabetes and benefitted millions of patients worldwide. During their visit, they met with Dario Alessi and Miratul Muqit to hear about the latest research developments into better understanding Parkinson's disease and Philip Cohen who undertook seminal work in diabetes research to elucidate the function of insulin and delineate its signalling pathway. Finally they met with Mike Ferguson to hear how about the work of the Drug Discovery Unit and the university's links to industry. |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.ppu.mrc.ac.uk/news/pioneer-digital-blood-glucose-meter-technology-visits-mrc-ppu |
| Description | Pursuing a breakthrough for Parkinson's |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Pursuing a breakthrough for Parkinson's |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.dundee.ac.uk/stories/pursuing-breakthrough-parkinsons |
| Description | Radio interview with Tay fm |
| 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 | Media (as a channel to the public) |
| Results and Impact | Conducted a Radio interview with local station Tay FM to discuss the recent press release by University of Dundee, titled "Dolly scientist backs research drive to tackle Parkinson's disease" |
| Year(s) Of Engagement Activity | 2018 |
| Description | Rallying to the Challenge - a general discussion |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | On Wednesday 8th September, myself, Miratul Muqit and Esther Sammler held a recorded a general discussion with Marc Van Greiken and Helen Matthews for the Cure Parkinson's trust on the research that we are doing in Dundee. This talk will be shown at a special 2021 conference for people with Parkinson's called "Rallying" that will have a worldwide audience. Rallying is a meeting for people with Parkinson's with the agenda designed by and with people living with Parkinson's. It is based on the Grand Challenges which were in person meetings held at the Van Andel Institute in Michigan. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://cureparkinsons.org.uk/rallying-to-the-challenge-2021/ |
| Description | Visit from Annie MacLeod, Scotland Director for Parkinson's UKs |
| 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 | Industry/Business |
| Results and Impact | Annie MacLeod, Scotland Director for Parkinson's UK visit our lab on Thursday 7th March. The purpose of Annie's visit was to find out more about our research. Annie also had a tour of our labs as well as meeting with myself, Miratul Muqit and Esther Sammler. |
| Year(s) Of Engagement Activity | 2019 |