The signaling pathways that regulate the production of pro-inflammatory cytokines

Lead Research Organisation: MRC Protein Phosphorylation Unit

Abstract

Infection by bacteria or viruses stimulates the immune system to produce pro-inflammatory cytokines and interferons, the substances that combat these pathogens. However, this defence mechanism is a double-edged sword because the uncontrolled production of cytokines and interferons can cause chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, as well as autoimmune diseases such as Multiple Sclerosis and Type 1 diabetes. For these reasons, the development of drugs that prevent the overproduction of cytokines and interferons is extremely important. My research group focuses on working out exactly how the immune system produces cytokines and interferons in response to infection. Our recent work has identified several enzymes that are attractive targets for the development of drugs to treat inflammatory and autoimmune diseases and in collaboration with MRC Technology, we have been involved in helping to develop a drug that suppresses interferon production. We have also made significant progress towards understanding how an unusual protein modification called Lys63-linked polyubiquitylation is involved in controlling cytokine production.

Technical Summary

Aims 1. To dissect the protein kinase cascades activated proinflammatory cytokines, infection and cellular stresses. 2. Elucidation of the physiological roles of each protein kinase that participates in this process. Plan of Investigation The techniques of protein chemistry, enzymology, cell biology, molecular biology, immunology and mouse genetics are being used to elucidate the molecular mechanisms by which infection by bacteria and viruses stimulate the production of pro-inflammatory cytokines, interferons and chemokines and why the deregulation of these pathways causes immunodeficiency diseases, increased susceptibility to bacterial infection, inflammatory diseases like Rheumatoid Arthritis and Crohns disease and autoimmune diseases such as Lupus. Our recent research has helped to elucidate the intracellular pathways that control the production of pro-inflammatory cytokines and interferons and pinpointed protein kinases that are attractive targets for the development of drugs to treat these diseases. Scientific/Medical and Commercial Opportunities Drugs that inhibit the protein kinases in these pathways may be efficacious for the treatment of chronic inflammatory diseases. Indeed such efficacy has already been demonstrated in some cases. These drugs are, however, likely to have additional/alternative uses; for example to treat cancer, or prevent tissue rejection during organ transplants. We facilitate the development of protein kinases inhibitors to treat disease through a collaboration between our MRC Unit and six of the worlds major Pharmaceutical companies that started in 1998. We have also been collaborating with MRC Technology to help them develop a new drug that suppresses interferon production. In addition, many of the reagents that we have developed are marketed by Millipore. This provides the Unit with significant revenue to support its research, and another benefit of this relationship was the setting up of a new company (Upstate Discovery Ltd) in Dundee, that now employs 70 people.

Publications

10 25 50
 
Description Founding of the Scottish Institute for Cell Signalling
Geographic Reach Asia 
Policy Influence Type Influenced training of practitioners or researchers
Impact My suggestion to set up a Scottish Institute for Cell Signalling was adopted in the election manifesto's of the Scottish Labour Party and the Scottish National Party and adopted by the latter when they won the election. £10million was awarded from October 2008 to September 2013 to set up a Protein Ubiquitylation Unit as the first division of the Scottish Institute for Cell Signalling. My interest in developing this area stemmed directly from my own research programme on the signalling pathways that regulate the production of proinflammatory cytokines.
 
Description MRC Programme Grant
Amount £1,456,000 (GBP)
Funding ID MR/K000985/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2013 
End 03/2018
 
Title MRC Technology compounds that inhibit the protein kinase TBK1 
Description Small organic molecule. 
Type Of Material Technology assay or reagent 
Year Produced 2011 
Provided To Others? Yes  
Impact Pubmed 19307177 
URL http://www.ncbi.nlm.nih.gov/pubmed/21138416
 
Title Protein kinases 
Description Since 2006, The National Centre for Kinase Profiling has added 88 new protein kinases to its profiling panel bringing the total number in the panel to 140. 
Type Of Material Technology assay or reagent 
Year Produced 2008 
Provided To Others? Yes  
Impact The protein kinases that we have provided to the five pharmaceutical companies with whom we collaborate in the Division of Signal Transduction Therapy have been used to launch many new drug discovery programmes, particularly in the field of cancer. Several drugs have been developed that have entered human clinical trials. Kinase Profiling has become a £100M per annum industry. 
 
Description Demonstration of abnormal expression of the protein kinase ERK5 in prostate cancer 
Organisation Newcastle University
Department Northern Institute for Cancer Research Newcastle
Country United Kingdom 
Sector Academic/University 
PI Contribution My laboratory provided the DNA clones and expression vectors encoding ERK5 and its activator MEK5, as well as antibodies encoding ERK5 and a compound that inhibits MEK5 that were required for this study. We also provided our collaborator, Dr H. Y. Leung, with advice throughout the study.
Collaborator Contribution The collaborators demonstrated the overexpression of MEK5 and ERK5 and nuclear localization of ERK5 in prostate cancer patients with poor disease-specific survival.
Impact Pubmed 18071319 This study suggested that drugs that switch off MEK5 or ERK5 activity may have therapeutic value for the treatment of prostate cancer.
Start Year 2006
 
Description Determination of the 3-dimensional structure of TAB1 
Organisation University of Dundee
Department College of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution My laboratory suggested this collaboration to Professor Daan van Aalten in the College of Life Sciences at the University of Dundee, produced large amounts of purified protein required for the study and performed all the enzyme assays. Daan van Aalten's group crystalized TAB1, a regulatory subunit of the protein kinase TAK1 and solved the 3-dimensional structure.
Collaborator Contribution Daan van Aalten is an X-ray crystallographer and his expertise in this area was essential to solve the structure of TAB1
Impact Pubmed 16879102 The structure of TAB1 revealed that it was an inactive pseudo-phosphatase related to the PPM subfamily of serine/threonine phosphatases. To my knowledge, this is the first pseudo-phosphatase related in structure to serine/threonine protein phosphatases.
Start Year 2006
 
Description Development of drugs that inhibit the protein kinases TBK1 and IKKepsilon 
Organisation MRC-Technology
Department MRCT Centre for Therapeutics Discovery (CTD)
Country United Kingdom 
Sector Academic/University 
PI Contribution My laboratory identified the compound BX795, first potent and relatively specific inhibitor of the protein kinase TBK1 and the closely related IKKepsilon. We suggested the collaboration to MRC Technology.
Collaborator Contribution Medicinal chemists at MRC Technology modified BX795 extensively to develop more potent and more drug-like inhibitors of TBK1 and IKKepsilon that may have therapeutic potential for the treatment of cancer and inflammatory diseases.
Impact The collaboration has led to the development of compounds that are more specific inhibitors of TBK1 and IKKepsilon and that have improved drug-like qualities. The collaboration represents MRC Technology's most advance small molecule drug discovery programme. We used the compound BX795 to advance our understanding of the physiological role and regulation of TBK1. Pubmed 19307177
Start Year 2007
 
Description Development of inhibitors of the kinases TAK1, SIK, LRRK2, IRAK4 and IRAK1 
Organisation Harvard University
Department Nathanael Gray Laboratory
Country United States 
Sector Academic/University 
PI Contribution My research team assesses the specificities of the compounds synthesised in the collaborator's laboratory and tests their effects on immune cells.
Collaborator Contribution The collaborator has provided chemical inhibitors of several protein kinases in the innate immune system that have been important research tools that have allowed me to advance understanding of the regulation of the innate immune system.
Impact Goh, E.T.H., Arthur,J.F.C., Cheung, P.C.F., Akira, S., Toth, R. and Cohen, P. (2011) Identification of the protein kinases that activate the E3 ubiquitin ligase Pellino 1 in the innate immune system. Biochem. J. published on-line October 18th Dzamko,N., Inesta-Vaquera, F., Zhang,J., Xie, C., Cai, H., Arthur,S., Tan, L., Choi, H., Gray, N., Cohen, P., Pedrioli, P., Clark, K. and Alessi, D.R. (2012) The IkappaB Kinase Family Phosphorylates the Parkinson's Disease Kinase LRRK2 at Ser935 and Ser 910 during Toll-Like Receptor Signaling. PloS one 7, pp. e39132 Clark,K., MacKenzie, K.F., Petkevicius, K., Kristariyanto, Y., Zhang, J., Choi, H.G., Peggie, M., Plater, L., Pedrioli, P.G., McIver, E., Gray, N.S., Arthur, J.S. and Cohen, P. (2012). Phosphorylation of CRTC3 by the salt-inducible kinases controls the interconversion of classically activated and regulatory macrophages. Proc Nati Acad Sci USA 109, pp. 16986-16991 Lopez-Pelaez, M., Lamont, D.J., Peggie, M., Shpiro, N., Gray, N.S. and Cohen, P. (2014). Protein kinase IKKbeta-catalyzed phosphorylation of IRF5 at Ser462 induces its dimerization and nuclear translocation in myeloid cells. Proc Natl Acad Sci USA 111, pp. 17432-17437 Tan,L., Nomanbhoy, T., Guurbani, D., Patrricelli, M., Hunter, J., Geng, J., Herhaus, L., Zhang, J., Pauls, E., Ham, Y., Choi, H.G., Xie, T., Deng, X., Buhrlage, S.J., Sim, T., Cohen, P., Sapkota, G., Westover, K.D. and Gray, N.S. (2015) Discovery of Type II Inhibitors of TFGbeta-Activated Kinase 1 (TAK1) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 2 (MAP4K2). J Med Chem 58, pp. 183-196
Start Year 2011
 
Description Discovery of NPM1 as a novel substrate for the protein kinase CDK6 activated by the Kaposi's sarcoma herpes virus D-type cyclin 
Organisation Institute of Cancer Research UK
Country United Kingdom 
Sector Academic/University 
PI Contribution My laboratory developed a novel method for identifying the substrates of protein kinases, termed KESTREL. Maria Cuomo, a student in the laboratory of Dr Sybylle Mittnacht, spent several months exploiting this technology in collaboration with Axel Knebel, one of my Postdoctoral Fellows. These studies identified several novel substrates for the Karposi cyclin D-CDK6 complex, one of which was NPM1.
Collaborator Contribution Maria Cuomo continued the project when she returned to London which led to an understanding of how NPM1 phosphorylation contributes to cancer driven by the Karposi sarcoma virus.
Impact Pubmed 18454140 The paper showed that NMP1 phosphorylation leads to p53-driven apoptosis and represents a checkpoint mechanism that prevents the accumulation of cells with supernumerary centrosomes. The study provided evidence that abnormal chromosome segragation in Karposi-infected cells is a direct consequence of NPM1 phosphorylation and that this leads to genomic instability that contributes to tumour formation induced by this virus.
Start Year 2006
 
Description Discovery of an improved method for embryonic stem cell self-renewal 
Organisation Wellcome Trust
Department Wellcome - MRC Cambridge Stem Cell Institute
Country United Kingdom 
Sector Academic/University 
PI Contribution My laboratory suggested, synthesised and provided the protein kinase inhibitors required for this study, namely the GSK3 inhibitor, CT99021 and the MEK1 and MEK5 inhibitors, PD184352 and PD0325901.
Collaborator Contribution Austin Smith and his research group carried out all the experimental work with the protein kinase inhibitors that I provided and which lead to the important technical advance mentioned above.
Impact Pubmed 18497825 The paper delineated the minimal requirements for mouse embryonic stem cell renewal and provided a defined platform for the precise description and dissection of the pluripotent state. It showed how embryonic stem cell renewal can be achieved inexpensively without any need for the addition of Leukaemia Inhibitory Factor. This represents a major technical advance in the field.
Start Year 2007
 
Description Discovery that the protein kinase Tpl-2 plays an essential role in processing pre-TNFalpha to the mature secreted form of this pro-inflammatory cytokine 
Organisation Medical Research Council (MRC)
Department MRC National Institute for Medical Research (NIMR)
Country United Kingdom 
Sector Academic/University 
PI Contribution My laboratory carried out nearly all the experimental work that lead to this discovery.
Collaborator Contribution The collaborators at NIMR, Anne O'Garra and Steven Ley, provided the Tpl-2 deficient mice required for part of the study and also measured the level of mRNA encoding pre-TNFalpha and the amount of TNF secreted in bone marrow-derived macrophages from wild type and Tpl-2 deficient mice after stimulation with bacterial lipopolysaccharide.
Impact The research discovered how the processing of pre-TNFalpha was regulated and provided further evidence that the protein kinase Tpl-2 is an attractive target for the development of anti-inflammatory drugs. The paper was selected as the Editor's Choice by Science Signaling, Vol 1, issue 2, p ec15. Pubmed 18187448
Start Year 2007
 
Description EU Framework Programme 6 on Protein Kinases - Novel Drug Targets of the Post Genomic Era 
Organisation European Commission
Department EC FP6 Collaborative Projects
Country European Union (EU) 
Sector Academic/University 
PI Contribution My research group carried out all the protein kinase profiling required by the participating laboratories involved in the Programme.
Collaborator Contribution The collaborators synthesised the compounds that were sent to us for kinase profiling.
Impact Pubmed 17032739, 18588507 and 17850214 Pagano et al (2007) Chembiochem. 8, 129-139 During this collaboration, we have helped ten different laboratories involved in the collaboration to define the specificities of the protein kinase inhibitors that they have developed.
 
Description Identification of a new transcriptional co-activator regulated by p38 MAP kinase 
Organisation Spanish National Cancer Research Center
Country Spain 
Sector Public 
PI Contribution My laboratory used yeast two-hybrid screening to identify a novel protein called p18Hamlet that interacted with p38 MAP kinase.
Collaborator Contribution My collaborator, Dr Angel Nebreda, identified the physiological role of p18Hamlet.
Impact p18Hamlet was found to be a transcriptional co-activator that stimulates p53-dependent apoptosis of cells showing that it is a new cell-fate regulator that links the p38 MAP kinase and p53 pathways and contributes to the establishment of p53-regulated stress responses. No pubmed number. Pubn details are: uadrado, A., Lafarga, V., Cheung, P. C. F., Dolado, I., Llanos, S., Cohen, P. and Nebreda, A. R. (2007). A new p38 MAP kinase-regulated transcriptional coactivator that stimulates p53-dependent apoptosis. EMBO J. 26, pp. 2115-2126
Start Year 2006
 
Description Protein kinase profiling for MRCT 
Organisation MRC-Technology
Department MRCT Centre for Therapeutics Discovery (CTD)
Country United Kingdom 
Sector Academic/University 
PI Contribution Protein kinase profiling of the compounds developed by MRC Technology
Collaborator Contribution MRC Technology developed more selective and drug like derivatives of BX 795, a compound that we identified as a potent inhibitor of the protein kinase TBK1. The compounds developed by MRCT have been very important in identifying novel physiological roles for TBK1.
Impact Pubmed 19307177
Start Year 2007
 
Description Role of the E3 ubiquitin ligase Pellino in regulating innate immunity 
Organisation Nanyang Technological University
Department Division of Molecular Genetics and Cell Biology
Country China 
Sector Academic/University 
PI Contribution My research team exploited an antibody and information provided by the collaborator to discover that the E3 ubiquitin ligase Pellino is activated in response to bacterial and viral infection and that it plays a key role in the production of Type I interferons.
Collaborator Contribution The collaborator provided an antibody and unpublished information
Impact Smith, H., Liu, X.Y., Dai, L., Xi, J., Goh, E.T.H., Chan, A.T., Xi, J., Seh, C.C., Qureshi, I.A., Lescar, J., Ruedl, C., Gourlay, R., Morton, S., Hough, J., McIver, E., Cohen, P. and Cheung, P. (2011) Biochem.J. 434, 537-548. The role of TBK1 and IKKepsilon in the expression and action of Pellino1 Enesa, K., Ordureau, A., Smith, H., Barford, D., Cheung, P.C.F., Patterson-Kane, J., Arthur, J.C. and Cohen, P. (2012) J.Biol. Chem. 287, 34825-34835. Defective production of type 1 interferons in mice expressing an E3 ligase-deficient mutant of Pellino1
Start Year 2010
 
Title A SIK inhibitor for use in a method of treating and inflammatory and/or immune disorder 
Description We have discovered a key role for the SIK subfamily of protein kinases in controlling the production of pro-inflammatory and anti-inflammatory cytokines. SIK inhibitors switch macrophages from the pro-inflammatory M1 phenotype to the M2b/2c regulatory phenotype that is thought to be critical for the resolution of inflammation 
IP Reference WO2013136070 
Protection Patent application published
Year Protection Granted 2013
Licensed No
Impact Pharmaceutical companies that I collaborate with have initiated programmes to explore the therapeutic potential of SIK inhibitors.
 
Title Anti-Inflammatory Agents 
Description Kris Clark and I, the inventors on the patent, discovered that the SIK subfamily of protein kinases restrict the production of the anti-inflammatory cytokine IL-10 and the formation of regulatory macrophages. SIK inhibitors greatly elevate the levels of IL-10, suppress the production of pro-inflammatory cytokines and switch macrophages to the regulatory M2 phenotype. SIK inhibitors are therefore novel and attractive targets for the development of improved anti-inflammatory drugs. 
IP Reference GB1204384.0 
Protection Patent application published
Year Protection Granted 2012
Licensed No
Impact Pharmaceutical companies with whom we collaborate have shown great interest in this finding and requested and were granted a nine-month delay in its submission for publication. we have started a programme to develop drugs that inhibit SIK specifically in collaboration with the Drug Discovery Unit at the University of Dundee
 
Title Development of novel inhibitors of the protein kinase TBK1 
Description My research group identified BX795 as a potent and relatively specific inhibitor of the protein kinase TBK1. MRC Technology have modified this molecule to create compounds that are more specific and with improved drug-like properties and have filed patents to protect these new structures. 
IP Reference WO2009122180 
Protection Patent granted
Year Protection Granted 2009
Licensed No
Impact The use of this molecule has led my research group to discover that TBK1 is activated by a novel 'upstream' protein kinase and that it regulates a feedback control loop that controls its own activation.
 
Title Identification of Tetrahydrocyclopentacridines as kinase inhibitors 
Description Novel inhibitors of particular protein kinases were identified that may have therapeutic potential as anti-cancer agents. 
IP Reference WO2009090623 
Protection Patent application published
Year Protection Granted 2009
Licensed No
Impact None
 
Title Identification of novel inhibitors of members of the PIM sub-family of protein kinases 
Description Novel pyrrolo[2, 3-A] carbazoles were developed and shown to be specific inhibtors of PIM kinases. 
IP Reference WO2010000978 
Protection Patent application published
Year Protection Granted 2010
Licensed No
Impact None
 
Title Novel inhibitors of TBK1 "Compound" 
Description Development of novel selective inhibitors of the protein kinase TBK1 
IP Reference US2010056524 
Protection Patent granted
Year Protection Granted 2010
Licensed No
Impact None
 
Title Inhibitors of the protein kinase TBK1 
Description Potent and specific inhibitor of TBK1 with therapeutic potential for the treatment of chronic inflammatory disease and/or cancer. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2009
Development Status On hold
Impact Nothing further to add. 
 
Title Proteins and antibodies 
Description My research has generated a large number of proteins and antibodies that are marketed by companies based in the UK (Abcam, Merck-Millipore and Ubiquigent Limited). These products are useful to researchers studying the role of protein phosphorylation and protein ubiquitylation in cell regulation and human disease. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Market authorisation
Year Development Stage Completed 2006
Development Status Under active development/distribution
Impact The products have generated significant revenue that have been used to enhance the research of the Unit and to furbish laboratory space for the Unit. They have also led to the formation of two spin out companies in Dundee, Merck-Millipore and Ubiquigent Limited. 
 
Company Name Ubiquigent Limited 
Description The company has been set up to market reagents, assays, services and technologies developed by the Protein Ubiquitylation Unit of the Scottish Institute for Cell Signaling which was set up as a result of my research into the role of ubiquitylation in studying the innate immune system.; http://www.ubiquigent.com 
Year Established 2009 
Impact MRC Technology holds 10% of the equity in Ubiquigent Limited.
Website http://www.ubiquigent.com/
 
Description 8th World Conference on Waldenstrom's Lymphoma 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact On the evening of August 16th Philip Cohen gave the closing lecture of the 8th International Workshop on Waldenstrom's Lymphoma in the Churchill rooms of the Houses of Parliament in London. Waldenstrom's lymphoma is caused by mutations in the protein MyD88, and 95% of the patients who are afflicted by this disease express the same mutant in which the leucine residue at position 265 is changed to proline. MyD88 is an essential adaptor protein in the signalling networks that are triggered by the binding of bacterial and viral components to Toll-Like Receptors or by the interaction of interleukins 1, 18 and 33 with their receptors.


Philip's talk to an audience that mainly comprised patients with Waldenstrom's lymphoma, their physicians, relatives and friends, focused on how MyD88 was discovered, and its key role in the innate immune system that is vital for protection against infection by microbial pathogens, especially during childhood. He also explained how the hyper-activation of the MyD88-dependent signalling network can lead to autoimmune diseases, such as lupus, and how its constitutive activation caused by the MyD88[Leu265Pro] mutation leads to lymphoma. The talk was followed by a formal dinner in the Churchill rooms, at which Philip and Tricia Cohen were the guests of honour.
Year(s) Of Engagement Activity 2014
 
Description Discussion with Minister 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Policymakers/politicians
Results and Impact My PhD student, Hosea Handoyo, who is from Indonesia, talked to the Indonesian Deputy Minister of Research and Technology about cell signaling.

Not yet.
Year(s) Of Engagement Activity 2009
 
Description Dundee Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Regional
Primary Audience Schools
Results and Impact My steudent Hosea Handoyo demonstrated an exhibit at the Dundee Science Festival

Hundreds of enthusiastic schoolchildren attended
Year(s) Of Engagement Activity 2010
 
Description Edinburgh International Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Schools
Results and Impact My student Hosea Handoyo demonstrated an exhibit at the Edinburgh International Science Festival

Schoolchildren seemed very interested
Year(s) Of Engagement Activity 2010
 
Description Interview with ZDF (German National Public Broadcasting) Regarding Scottish Referendum 
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 ZDF wished to interview Professor Cohen regarding the risks for life sciences in an independent Scotland for their European affairs programme that wished to discuss an economic case for and against independence.


Sir Philip's signature on an open letter and viewpoints expressed, while his own, brought to light in the general public, the potential deleterious impact a 'Yes' vote would have had upon Scottish scientific research funding.
Year(s) Of Engagement Activity 2014
URL http://www.zdf.de/ZDFmediathek#/hauptnavigation/startseite
 
Description New Drugs for the 21st Century 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact "Philip Cohen gave a talk about kinase drug discovery to the Scotland International Group at the Gleneagles Hotel Scotland on Friday November 29th 2013. Entitled "New Drugs for the 21st Century". The audience of 60 included the CEOs and CFOs of 20% of the UK's FTSE 100 companies, the Brazilian and Russian Ambassadors, the former UK Ambassador to the USA, the former Secretary General of NATO), Sir the former head of UK Government Operations, and Scotland's only two billionaires."


Sir Philip's talk stimulated much discussion as he recounted the research being undertaken in Dundee and the potential of many of the targets torwards therapeutic development.
Year(s) Of Engagement Activity 2014
 
Description Public Lectures 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact I gave public lectures at the University of Washington, Seattle, USA and at the Dundee Science Festival. Several hundred members of the general public attended each lecture.

As a result of the lecture at the University of Washington a Wikipedia was developed about the Division of Signal Transduction Therapy in which the National Centre for Kinase Profiling is located. After the Dundee Science Festival lecture several schoolchildren who were in the audience came to talk to me and indicated that they hoped to make science their career.
Year(s) Of Engagement Activity 2010
 
Description Scotland: For Richer or Poorer? 
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 Public/other audiences
Results and Impact Professor Sir Philip Cohen will be featured on Robert Peston's BBC2 Documentary 'Scotland: For Richer or Poorer' airing tonight at 9pm on BBC2. How will independence affect Dundee's reputation for excellence in life sciences?


Sir Philip's signature on an open letter and viewpoints expressed, while his own, brought to light in the general public, the potential deleterious impact a 'Yes' vote would have had upon Scottish scientific research funding.
Year(s) Of Engagement Activity 2014
URL http://www.bbc.co.uk/iplayer/episode/b049b89z/scotland-for-richer-or-poorer
 
Description Scottish Referendum - Open Letter 
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 "A group of eminent Scottish medical experts have warned that independence would seriously damage research funding for Scotland's universities and medical schools.

The open letter from 14 experts, including senior staff from all five of the country's main medical schools, said they had ""grave concerns"" that Scotland's world-leading biomedical and life sciences research would suffer if Scotland ""sleepwalks"" into leaving the UK.

The letter, coordinated by Sir David Carter, a former chief medical officer in Scotland, said Scottish universities did disproportionately well out of the UK's research funding system and from the UK's charitable and medical foundation grants.
"


Sir Philip's signature on an open letter and viewpoints expressed, while his own, brought to light in the general public, the potential deleterious impact a 'Yes' vote would have had upon Scottish scientific research funding.
Year(s) Of Engagement Activity 2014
URL http://www.theguardian.com/politics/2014/may/23/scottish-independence-research-funding-medical-exper...
 
Description Sharing Science, a public outreach programme 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact My student, Hosea Handoyo, went to the Scottish Association for Marine Science Open Day in Oban and to both the Dundee and Edinburgh Science Centres under this programme to talk to the general public about cell signaling. He also went to the Dundee Science Centre to talk to the general public about how inhibitors of protein kinases can be used to treat diseases.

Generated considerable interest in the work of the MRC Protein Phosphorylation Unit among school children and the general public.
Year(s) Of Engagement Activity 2009
 
Description Student's important protein discovery could help fight cancer 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Jiazhen Zhang, a research student in Professor Sir Philip Cohen's laboratory at the University of Dundee, has uncovered how the protein complex, called NF-?B, is activated. The results are published in July, 2014.


Research being undertaken in the Cohen lab was discussed by the broader lay community in an effort to share the impact of these studies
Year(s) Of Engagement Activity 2014
URL http://news.stv.tv/tayside/282195-jiazhen-zhang-at-university-of-dundee-publishes-research-on-nf-b/
 
Description Two lectures to the general public 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The lectures took place at the University of Washington, Seattle, USA in April and at the Dundee Science Festival, Dundee, Scotland in October. Several hundred members of the general public attended each lecture.

Several schoolchildren who attended the public lecture in Dundee talked to me after the lecture and said that they wished to make their career in science. As a result of the lecture at the University of Washington a Wikipedia was set up on the MRC Protein Phosphorylation Unit's groundbreaking collaboration with the pharmaceutical industry called the Division of Signal Transduction Therapy.
Year(s) Of Engagement Activity 2010