TGFß and Wnt signalling during development and human disease

Lead Research Organisation: University of Dundee
Department Name: UNLISTED

Abstract

Our lab is interested in understanding how the TGFß and Wnt signalling pathways are regulated during development and in adult cells and how their misregulation causes human diseases. These pathways control a plethora of cellular processes and are often broken in many diseases, including skin and bone disorders, fibrosis and cancer. Therefore, a better understanding of their molecular regulation will lead to new opportunities for therapeutic intervention.
Recently, we have identified a novel role for the FAM83 family of uncharacterised proteins in the regulation of CK1 family of Ser/Thr protein kinases. The CK1 family is known to control many cellular processes, including cell cycle progression, circadian rhythm, DNA-damage repair and Wnt and Shh signalling, but how it is regulated to impact so many cellular processes has remained a mystery. We want to understand precisely how the FAM83 family controls the activity, subcellular distribution and substrate specificity of the CK1 family.

Technical Summary

Signal transduction pathways triggered by the transforming growth factor beta (TGFß), bone morphogenetic protein (BMP) and Wnt ligands control a plethora of cellular processes throughout metazoan development and adult life. In humans, aberrations in these signalling cascades result in many diseases, including skin and bone disorders, fibrosis and cancer. My group studies the molecular mechanisms that underpin the regulation of TGFß and Wnt signalling pathways. We identified the PAWS1 protein that is a member of the FAM83 family of previously uncharacterised proteins, and showed that it is not only a modulator of BMP signalling but also a critical anchor of casein kinase (CK) 1? that streamlines Wnt signalling. Excitingly, our work indicates that other FAM83 family members are also key anchors for different CK1 isoforms. These findings represent a significant advance in our understanding of how the CK1 family of constitutively active Ser/Thr protein kinases is regulated in cells, in order to control diverse cellular processes.

People

ORCID iD

Related Projects

Project Reference Relationship Related To Start End Award Value
MC_UU_00018/1 01/04/2018 31/03/2024 £4,394,000
MC_UU_00018/2 Transfer MC_UU_00018/1 01/04/2018 31/03/2024 £2,542,000
MC_UU_00018/3 Transfer MC_UU_00018/2 01/04/2018 31/03/2024 £3,121,000
MC_UU_00018/4 Transfer MC_UU_00018/3 01/04/2018 31/03/2024 £2,751,000
MC_UU_00018/5 Transfer MC_UU_00018/4 01/04/2018 31/03/2024 £3,744,000
MC_UU_00018/6 Transfer MC_UU_00018/5 01/04/2018 31/03/2024 £2,520,000
MC_UU_00018/7 Transfer MC_UU_00018/6 01/04/2018 31/03/2024 £2,557,000
MC_UU_00018/8 Transfer MC_UU_00018/7 01/04/2018 31/03/2024 £2,128,000
 
Description AMPK-AdPROM
Amount £130,000 (GBP)
Organisation University of Copenhagen 
Sector Academic/University
Country Denmark
Start 03/2021 
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Description Cunningham Trust PhD studentship
Amount £83,236 (GBP)
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Description ERC
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Description GSK-DSTT Postdoctoral Fellowship
Amount £240,000 (GBP)
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Country United Kingdom
Start 09/2019 
End 12/2019
 
Description MJFF-Ubiquitin
Amount £367,000 (GBP)
Organisation Michael J Fox Foundation 
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Country United States
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Description MRC Flexible Supplement Award
Amount £23,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2018 
End 05/2019
 
Description MRC Flexible Supplement Award
Amount £23,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 01/2020
 
Description Medical Research Scotland PhD studentship
Amount £106,000 (GBP)
Funding ID PhD-1170-2017 
Organisation Medical Research Scotland 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2018 
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Description Novel Approach to Rewiring Cell Signalling
Amount £1,702,374 (GBP)
Organisation Amgen Inc 
Sector Private
Country United States
Start 12/2021 
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Description PRIND - Govt of Belgium
Amount € 535,504 (EUR)
Organisation Janssen Pharmaceutica NV 
Sector Private
Country Belgium
Start 10/2020 
End 04/2023
 
Description Alex Bullock 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution .
Collaborator Contribution Structural expertise on FAM83 proteins
Impact .
Start Year 2014
 
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 Inc
Country United States 
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 David Kelsell 
Organisation Queen Mary University of London
Department Blizard Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution Testing pathogenic FAM83G mutations in our signalling systems
Collaborator Contribution identification of pathogenic mutations and assessing patients
Impact .
Start Year 2016
 
Description Nathanael Gray 
Organisation Dana-Farber Cancer Institute
Country United States 
Sector Hospitals 
PI Contribution testing kinase inhibitors in our biological systems
Collaborator Contribution generating and providing kinase inhibitors
Impact .
Start Year 2014
 
Description Partnership with Amgen, Alessio Ciulli and Adrian Saurin 
Organisation Amgen Inc
Country United States 
Sector Private 
PI Contribution Together with Alessio Ciulli and Adrian Saurin, we were awarded a grant to investigate targeted dephosphorylation of phospho-proteins. The preliminary data used for this award and proof-of-concept data came from my lab.
Collaborator Contribution Alessio Ciulli is a world-leading expert in bivalent molecules and Adrian Saurin is an expert in phosphatases.
Impact In progress
Start Year 2022
 
Description Precision control of protein dosage in vivo - MRC Mouse Genetics Network collaboration 
Organisation Medical Research Council (MRC)
Department MRC Human Genetics Unit
Country United Kingdom 
Sector Academic/University 
PI Contribution I was part of the grant application to the MRC Mouse Genetics Network Cluster application (led by Andrew Wood) to utilise targeted degradation systems in vivo.
Collaborator Contribution I contributed with the design of the degron construct to be utilised for the transgene to be introduced in mice and helped shape the application.
Impact In progress
Start Year 2022
 
Description Targeted Protein Degradation 
Organisation Janssen Pharmaceutica NV
Country Belgium 
Sector Private 
PI Contribution Joint funding award from the Belgian Government
Collaborator Contribution Two postdoctoral fellows working in my laboratory working on a joint project with Janssen
Impact In progress
Start Year 2020
 
Description 3-Minute Thesis 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Bill Carton, a PhD student from my lab, took part in University-wide 3-Minute thesis competition and won multiple awards. News Item published on the PPU website and Social media (Twitter/LinkedIN) platforms. He won multiple awards.
Year(s) Of Engagement Activity 2021
URL https://www.ppu.mrc.ac.uk/index.php/news/bill-carton-phd-student-sapkota-lab-lands-multiple-awards-u...
 
Description Biotechnology Young Entrepreneurs Scheme (YES) 2021 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact PPU PhD students (including Bill Carton from my lab) participated in and advanced to the finals of the Biotechnology Young Entrepreneurs Scheme (YES) 2021. News Item published on the PPU website and Social media (Twitter/LinkedIN) platforms. Won awards.
Year(s) Of Engagement Activity 2021
URL https://www.ppu.mrc.ac.uk/index.php/news/3-ppu-phd-students-advance-finals-biotechnology-young-entre...
 
Description Discovery Days Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact As newly promoted Professor, I was asked to deliver the public Discovery Days seminar organised by the University of Dundee. This seminar invites local general public, school pupils and university staff and students to listen to the talks delivered by newly promoted professors. The talk itself is also in Youtube and is accessible to the general public.
Year(s) Of Engagement Activity 2022
URL https://www.youtube.com/watch?v=Y3aMezC15uQ
 
Description Explorathon 'Science in Our Lives 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Abigail Brewer, a PhD student from my lab, took part in "Explorathon 'Science in Our Lives' Pecha Kucha Session". The target audience was the general public and the aim of the event was to provide the audience with a brief insight, through Pecha Kucha format talks (20 slides, each 20 seconds), into different research that is being conducted across Scotland. Abbie was invited to give a talk about my PhD research and so spoke about targeted dephosphorylation of proteins.
Year(s) Of Engagement Activity 2021
 
Description Hosting a High School student in the Lab 
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 We hosted a high school (S4) pupil for a week in the lab. We will monitor whether the student decides to take up Scince at University.
Year(s) Of Engagement Activity 2017
 
Description Hosting high school pupils 
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 My lab hosted local high school students for work experience week. The students were exposed to a wide array of techniques in medical research and got an opportunity to interact with all the members of my lab about their research. At least one student notified me of her wish to apply for a biochemistry course for her University education.
Year(s) Of Engagement Activity 2022
 
Description I'm a scientist 
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 Bill Carton, PhD student from my lab, took part in the "I'm a Scientist" programme. It's an online website that pairs scientists up with local school classrooms so they can ask you questions.
Year(s) Of Engagement Activity 2021
 
Description Interview With Local Radio station Wave 102 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Following publication of one of our papers on PAWS1, I was interviewed by News segment of Wave 102, a tayside radio station.
Year(s) Of Engagement Activity 2018
 
Description Local Schools Outreach 
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 I was invited to talk to P1, P3 and P5 children from Barnhill Primary School about being a research scientist. I gave a talk in the respective classrooms, conducted few experiments with the children (using small liquid measurements) and did a question-answer session with the children.
Year(s) Of Engagement Activity 2018
 
Description MRC Festical of Medical Research Inside Out Science Open Day 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact MRC Festival of Medical Research Inside Out Science Open day involved researchers from the MRC Protein Phosphorylation and Ubiquitylation Unit (MRC PPU) and MRC Doctoral Training Programme students (from the Schools of Life Sciences and Medicine at the University of Dundee). The MRC Festival aimed to inform, inspire and stimulate thinking about medical research. Our event was held within the School of Life Sciences and involved seven table top engagement activities, five ten-minute accessible science talks given by PhD students and early career researchers, three lab tours and three videos about the scientific work of the Unit on loop with visitors. There were two new activities called Chromatography and Stem Cell Game trialled that were developed by MRC PPU staff and students plus previously developed activities. Prior to the open day event, a primary six class at Glebelands Primary School attended a 90 minute session to give valuable feedback on talks and new activities.

Members from my lab who participated were;
Luke Fulcher - PhD Student
Theresa Tachie-Menson - PhD Student

Overall, 129 members of public (generally family groups) were reached with 103 people visiting on the day, a further 24 Primary Six pupils and their two teachers who gave feedback on the new talks and activities ahead of the event.
The event met a number of the objectives and key messages from the 2018 - 2023 MRC Protein phosphorylation and ubiquitination Public Engagement and Communications Plan which were:

Communications Objectives
1) Generate interest in science as a career path for young people in Dundee to reveal opportunities and make science accessible.
2) Share the unit's research expertise with non-scientific communities to raise awareness of the importance of basic research in understanding health and disease.

Key Messages
1) Basic research is vital - before we can develop new medicines we first need to understand how the body works in health and disease.
2) MRC PPU is an outstanding environment to pursue phosphorylation or ubiquitylation research.
3) As scientists we value new ideas and are open to sharing our work with all who have an interest in it.

Feedback
The visitors to the event were a mixture of ages which included family groups (children under 16 years) and adults up to 70 years of age. Feedback indicated that they enjoyed themselves overall and said they would come to a similar event again. Highlights included a game developed on the topic of Stem Cells and the laboratory tours. Around a third of visitors polled had not attended a University of Dundee event before indicating we were reaching new audiences.
The talks in particular stimulated a number of questions from the audience such as:
• How long does it take for a cell to divide?
• What would happen if you lost all your amino acids?
• Is it only older people who get Parkinson's?
• What is it about not being obese that helps protect you from Alzheimer's?
• What does wildtype mean?

Participants reported having a positive experience, they all said they'd do it again and that they'd recommend a colleague take part too.
Year(s) Of Engagement Activity 2018
 
Description Media Coverage (KRAS degradation) 
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 Media (as a channel to the public)
Results and Impact On 15th July 2020, a press brief by the University of Dundee was released describing two back-to-back papers from my lab (https://www.dundee.ac.uk/stories/scientists-destroy-undruggable-cancer-causing-protein?utm_content=bufferb21b7&utm_medium=social&utm_source=linkedin.com&utm_campaign=buffer). This was picked up by several New Media outlets including the following:
https://www.thecourier.co.uk/fp/news/local/dundee/1442900/dundee-scientists-discover-how-to-destroy-undruggable-cancer-causing-protein/
https://www.fifetoday.co.uk/health/breakthrough-dundee-university-2915194
https://www.kirkintilloch-herald.co.uk/health/breakthrough-dundee-university-2915194
https://indianexpress.com/article/lifestyle/health/university-of-dundee-cancer-kras-6510964/
https://www.expresshealthcare.in/news/university-of-dundee-researchers-destroy-undruggable-cancer-causing-k-ras-protein/423434/
Year(s) Of Engagement Activity 2020
 
Description News Item PPU website and Social media (Twitter/LinkedIN) platforms (Karen Dunbar - publications) 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact We advertised Karen Dunbar's findings when the papers were published in Life Science Alliance.
Year(s) Of Engagement Activity 2021
URL https://www.ppu.mrc.ac.uk/index.php/news/karen-dunbar-sapkota-lab-mrc-ppu-uncovers-fam83f-mediator-c...
 
Description Participation in Patient Engagement Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact Parkinson's Exchanges: developing creative resources for exchanges between research and lived experience of Parkinson's Disease. Together with Miratul Muqit and Daksha Patel.
Year(s) Of Engagement Activity 2022
 
Description Participation in Patient Engagement Event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Patients, carers and/or patient groups
Results and Impact An event was organised between researchers working on Parkinson's disease and PD patients and their families, where researchers presented their work in lay language to pateints. This was an incredibly humbling experience that inspired all researchers to work towards understanding and tackling PD.
Year(s) Of Engagement Activity 2022
 
Description School Visit 
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 Careers in Science visit to Baldragon Academy, Dundee. The objective was to get students interested in a career in science, and potentially change their preconceived perceptions of scientists..
Year(s) Of Engagement Activity 2023
 
Description That's TV Scotland Interview Broadcast 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Media (as a channel to the public)
Results and Impact Cell Cycle Discovery : Coverage of our paper
Year(s) Of Engagement Activity 2019
URL https://www.facebook.com/watch/?v=522238835184862
 
Description Virtual Work experience (Molecular Biology) 
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 During the COVID-lockdown, a postdoctoral fellow from my lab (Sascha Roth), participated in a workshop explaining to local school pupils (S4-6) on molecular biology techniques and applications.
Year(s) Of Engagement Activity 2020
 
Description Work Experience Week 2019 
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 Schools
Results and Impact The Work Experience Week ran from July 29-August 2, 2019 for 21 S6 pupils from a variety of local secondary schools. As part of this week they took part in a careers speeding dating session, tours of various facilities, visits to the James Hutton Institute and the School of Medicine, ethics discussions, group presentations and four separate sessions of lab-based practical work.
My lab:
• hosted a small group of pupils for a 3-hour lab session, giving them hands-on experience in a working lab and answering questions about careers and study
• took part in the careers speed dating session, sharing my personal journey through study and work and answering questions
• led a tour around facility for groups of pupils
• led an interactive session on the use of animals in research
Feedback was overwhelmingly positive, including one student who said: "I have learned that science is both independent and requires a team spirit because there is the aspect of freedom working on a topic of interest but also that scientists help each-other and collaborate."
Year(s) Of Engagement Activity 2019