A Systems Approach for the Fragment-Based Development of Selective Chemical Probes of Bromodomain Function
Lead Research Organisation:
University of Dundee
Department Name: School of Life Sciences
Abstract
A key cellular mechanism for regulating expression of the genetic information stored in DNA is by mean of protein 'factors' that gene transcription. One group of such proteins affects gene expression levels by 'reading' epigenetics marks, i.e. reversible chemical modifications that are installed on other proteins that associate with DNA to form the highly compacted structure known as chromatin. A widely occurring modification is acetylation of lysine amino acids, which is specifically recognized by proteins that contain between one and six 'reader' domains called bromodomains. The human genome encodes 42 bromodomain containing proteins, giving a total number of 57 unique sequences that make up the bromodomain protein family. There is increasing evidence that link bromodomain proteins in various diseases, including cancer, however specific functions of many bromodomain proteins are yet unknown. Potent, cell-permeable small molecules that perturb the function of a biological target in a dose-dependent fashion are a powerful way to 'probe' the role of the target in a particular biological process as well as its association to disease and thus its therapeutic potential. Small molecules have several advantages over more traditional approaches involving gene knock outs or RNAi, including allowing spatial and temporal controls on the effect within a cell. However, identification of probe compounds can be laborious and often involves screening of large compound libraries. It can be challenging to develop 'tool compounds' that are not only sufficiently potent against a target protein but also highly selective so they do not bind to other similar proteins. This often hampers the successful application of chemical probes to establish a relationship between a molecular target and the biological consequences of modulating the target. Developing new approaches and tools to make advances in these areas would have an immediate impact in the field of chemical biology and for target validation in drug discovery. Recent years have seen the establishment of a novel, powerful approach to identify high quality binders against proteins. This involves screening libraries of molecules, so-called 'fragments', that are much smaller than those usually tested e.g. in 'high-throughput screening'. The binding modes of 'hits' identified from a fragment screen are characterized using protein structural techniques so their interactions with the protein are determined in details. Once several fragment hits are identified, the combined information on their interactions, on the nature of the binding site and knowledge of their chemistry can provide a basis for 'elaborating' these structures into more potent chemical probes. In the current proposal, we will combine fragment-based approaches with protein engineering, a technique to generate specific mutations on a protein by changing amino acids from one type to another. First we will elaborate bromodomain-targeting fragments by 1) 'growing' them to pick additional interactions with the binding site; 2) 'merging' fragments bound at overlapping sites at the acetyl-lysine binding pocket. This will generate tight binding ligands for bromodomains. Second we will elaborate these molecules to accommodate functional groups that chemically complement the mutation introduced in the binding site, e.g. filling space created by engineering a pocket, and/or 'clicking' the ligand covalently onto a cysteine. Such modified chemical probes should be highly selective for the mutant against wild-type or indeed any other bromodomain. Since the mutation can be rapidly introduced into any bromodomain protein and in a cell, the methods and tools that will be developed in this programme would allow a general strategy to chemically interrogate the biological function of bromodomain proteins at the system level. This approach could then be extended to study other reader domain systems as well.
Technical Summary
Bromodomains are a family of small modules found in histone acetyl transferases and other chromatin-associated proteins that play crucial roles in many cellular physiological pathways and are also implicated in disease. They specifically recognise acetyl-lysine post-translational modifications in histones amongst other proteins, thereby acting as readers of the epigenetic code. The human genome encodes 57 bromodomain sequences, however the biological function of many of these remains to be dissected. This proposal is centred on the applications of fragment-based chemical tools and engineering of bromodomain-histone interfaces to develop highly selective small molecule probes that can aid elucidation of the individual roles of bromodomains at the system level. The project will exploit fragment-based design, synthetic chemistry, protein X-ray crystallography and various biophysical techniques including AlphaScreen, NMR spectroscopy and isothermal titration calorimetry to identify and characterize small molecule fragments that bind at the acetyl-lysine binding site of bromodomains. Two interdependent lines of enquiry will then be followed. First, we will chemically elaborate the fragments using 'growing' and 'merging' approaches to improve their affinity as inhibitors of the bromodomain-histone interaction. Second, we will modify fragments and fragment-derived ligands to chemically complement mutations in the bromodomain-histone interface in ways that would allow chemical probes to bind preferentially to engineered bromodomains against wild-type bromodomains. The selectivity of the chemical probes will be tested against a panel of bromodomains in vitro, and studies on their cellular activities will also be conducted. Collectively these studies will advance our knowledge and understanding of the molecular and structural basis for selectivity of chemical probes targeting this conserved protein-protein interaction family.
Planned Impact
The research proposal aims to develop and apply fragment-based screening to the design of inhibitors of the human bromodomain-histone interaction, and to enable the development of such small molecules into highly selective chemical probes for individual bromodomains by combining the fragment approach with directed protein engineering at a system level. The work proposed is multidisciplinary, involving protein expression, purification and characterization, protein-peptide and protein-small molecule binding studies using biophysical techniques including NMR spectroscopy, ITC, and AlphaScreen, structural biology and organic synthesis. The ultimate aim of the project is to provide a novel, generally applicable approach to pin-point the individual roles of bromodomains and of their specific recognition of lysine acetylation, thus aiding elucidation of the function of bromodomain-containing transcription factors and chromatin remodelers in the human genome. Beneficiaries from the research include scientists in both industry and academia who are interested broadly in the fields of chemical and structural biology and drug design. It will impact biologists interested in epigenetics, chromatin structure, function and modifications, and gene regulation in physiology and disease. By stimulating wider use of multidisciplinary, systems and predictive approaches to bioscience, the work will impact a growing national and international community of synthetic and system biologists. These studies will also have strong impact on epigenetics target validation for drug discovery in many disease areas including inflammation, metabolism and cancer. This will be of interest to members within the Pharmaceutical Industry, within charities concerned with the threat of diseases and will influence policy-makers within government, national and international agencies in terms of showing that investment is being channelled into key areas that will underpin future drug discovery. By providing new tools to advance fundamental understanding in biological processes relevant to critical disease areas the research has therefore the potential to impact on the nation's health and economic competitiveness. Many beneficiaries will be direct 'users' of the research outputs, both immediately and in the longer term. Crystal structures of bromodomain-ligand complexes will be deposited in the PDB and in the SGC databases and will thus provide useful information to structural biologists, bioinformaticians and drug designers. Structures of chemical probes will be released and the compounds made available to the community upon request, meaning that many biologists studying chromatin structure, function and epigenetic modifications will be able to use these chemical tools to carry out experiments. The timescale for such impact is difficult to predict, but we expect that the developments in fragment-based screening approaches and concomitant work on manipulating bromodomain-histone interface to identify highly selective small molecule chemical probes will yield several compounds and new insights into the structural basis of bromodomain-histone target selectivity in the next 2-3 years. According to outcomes from studies in this work and allied programmes at validating potency and selectivity of molecules generated, we expect the research to inspire similarly directed targeting studies and embracing of related approaches and strategies in academia/industry soon after relevant publications emerge, also extending to other families of related reader domains e.g. chromodomains, Tudor and PHD fingers. We are also confident that the range of approaches that will be undertaken will provide the PDRA and RA appointees with a range of professional skills suited to career development in both academic and industrial settings, thereby maintaining and fostering national strengths in core underpinning disciplines such as molecular, chemical, cellular and structural biology.
Publications
Alessio Ciulli (Author)
(2014)
A novel approach to engineer selectivity of bromodomain chemical probes
in ChemMedChem
Alessio Ciulli (Author)
(2014)
A novel approach to engineer selectivity of bromodomain chemical probes
Baud MG
(2016)
New Synthetic Routes to Triazolo-benzodiazepine Analogues: Expanding the Scope of the Bump-and-Hole Approach for Selective Bromo and Extra-Terminal (BET) Bromodomain Inhibition.
in Journal of medicinal chemistry
Baud MGJ
(2014)
Chemical biology. A bump-and-hole approach to engineer controlled selectivity of BET bromodomain chemical probes.
in Science (New York, N.Y.)
Bond AG
(2020)
Stereoselective synthesis of allele-specific BET inhibitors.
in Organic & biomolecular chemistry
Bortoluzzi A
(2017)
Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains.
in The Biochemical journal
Cipriano A
(2020)
Targeting epigenetic reader domains by chemical biology.
in Current opinion in chemical biology
Title | Video of the Dundee-Messina project - Ciulli Lab |
Description | the video is being used to support the dissemination of the Dundee-Messina project funded by the MIUR programme Messaggeri della Conoscenza |
Type Of Art | Film/Video/Animation |
Year Produced | 2014 |
Impact | impact not yet realised - video just published online |
URL | https://www.youtube.com/watch?v=JFF7QN22yEI |
Description | 1) Bump and hole approach. In a recent breakthrough published in Science, my laboratory has demonstrated for the first time that it is possible to engineer in a controlled fashion exquisite selectivity of BET bromodomains chemical probes using a so-called "bump-and-hole" approach (Baud et al., Science 2014). This is per se a formidable achievement, unprecedented at targeting a PPI. Moreover, we applied the method to show that blockade of the first bromodomain alone is sufficient to displace a specific BET protein, Brd4, from chromatin. This has important implications for future drug design strategies against this target. Our discovery has made a broad impact, as demonstrated by attracting several research highlights in high-profile journals (Nature Chemical Biology, Nature Methods and Cancer Discovery Research Watch), and press releases e.g. from BBSRC Business magazine. It has also attracted attention by conference organizers (AC delivered a Featured Presentation to describe this discovery at the 10th Annual CHI Drug Discovery Chemistry conference in San Diego in April) and the pharmaceutical industry. A patent application related to examining the function of BET proteins using the technology was filed. More recently, we have built on our bump-and-hole approach to achieve selectivity for the second wild-type BET bromodomains of the BET family over the first bromodomains (Baud et al. J. Med. Chem. 2016). Following our breakthrough publications in Science (Oct. 2014) and J. Med. Chem. (Sept. 2015) of allele selective chemical genetic bump-and-hole approach to selective BET bromodomain inhibition, we worked to further develop and optimize the method. We identified and characterized more conservative and more functionally silent mutants than those initially investigated. We also designed, synthesized and characterized new improved bumped ligands, which have significantly enhanced the probe selectivity for mutant vs wild type (manuscript in preparation). We have applied the improved tool to address key questions on the individual roles of each bromodomain in a single protein, and of each individual BET protein from one another. To achieve this, we have established novel cell-based models for functional complementation/rescue studies, by replacing the endogenous wild-type BET protein with the mutant. We have published the optimization of this system in a recent article in the journal Chemical Science, 2018, 9, 2452 - 2468. We are now using CRISPR-Cas9 to knock-in the mutation first in cell lines in vitro, with the goal to ultimately enable the approach in animal models in vivo. 2) We have made important contributions to other areas as well, working in collaboration with Stefan Knapp (SGC, Oxford) and Rolf Boelens and Alexandre Bonvin (Utrecht). • By combining biophysical fragment-based screening and structure-guided optimization, we have tackled the bromodomain of BAZ2B, a protein of poorly characterized function considered to be one of the least druggable in the family (Ferguson et al., J. Med. Chem., 2013). This study described one of the first low-micromolar affinity compounds against a bromodomain outside of the BET subfamily, suggesting the entire human protein family may be druggable. • We have conducted structural and biophysical molecular recognition studies on bromodomain and PHD finger reader domains of BAZ2B and the related BAZ2A protein that has very recently been linked to prostate cancer. This work elucidated key structure-function relationships and molecular insights on binding hot spots by combining structural (protein NMR spectroscopy, X-ray crystallography, and SAXS of tandem domain proteins), biophysical (ITC, BLI), and computational (data-driven docking and molecular dynamics) approaches (Ferguson et al., Biochemistry 2014; Tallant et al., Structure 2015). |
Exploitation Route | by exploiting our chemical tools to ask many biological questions as well as interrogate their therapeutic potential |
Sectors | Healthcare,Pharmaceuticals and Medical Biotechnology |
URL | http://www.lifesci.dundee.ac.uk/groups/alessio-ciulli |
Description | The breakthrough discoveries made by our laboratory and collaborators of potent VHL ligands have led not only to several publications, but also two patents (US 2014356322 and WO 2013106646), and to the establishment of Yale spin-off Arvinas in the US and a Discovery Platform Unit (DPU) within GlaxoSmithKline Stevenage, UK. Such activity represents tangible output of Dr. Ciulli's research in terms of impact, innovation and commercial exploitation. Arvinas and the GSK DPU are pharmaceutical companies both focused on developing small molecule strategies aimed at degrading disease- causing cellular proteins, with a focus in oncology amongst other therapeutic areas. One breakthrough was the design of super-targeted inhibitors, which have exquisite selectivity for honing in on individual BET bromodomains (protein interaction modules that bind acetyl-lysine), without affecting the many other such domains in a cell. The trick was a novel `bump-and-hole' approach that matches the inhibitors to dual features of the target sites (Science, 2014, 346, 638-641). In a further twist, the Ciulli Lab developed a new class of compounds that do not just block BET proteins, but spark a process of degradation, which eventually destroys with exquisite selectivity the cognate protein (ACS Chem Biol, 2015, 10, 1770-1777). This is achieved by means of hetero-bifunctional molecules known as PROteolysis TArgeting Chimeric molecules (PROTACs) that targets the selected protein to the ubiquitin-proteosome degradation pathway using an E3 ligase ligand that the group had previously discovered (J Med Chem, 2014, 57, 8657-8663). Since proteins containing BET bromodomains play crucial roles in many cellular physiological pathways relevant to health and disease, the compounds have exciting potential to accelerate development of therapeutic drugs with minimal side effects and toxicity. Following these discoveries, Dr Ciulli and the University are engaged in confidential discussions to partner with pharmaceutical companies. Dr Ciulli and the UoD have filed two patents relating to the new approaches (patent number WO/2015/079259 http://www.freepatentsonline.com/WO2015079259A3.html; and Patent Application No. GB 1504314.4, Filing Date: March 13, 2015). |
First Year Of Impact | 2012 |
Sector | Healthcare,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |
Description | BBSRC ALERT14 High throughput bio-layer interferometry at Dundee |
Amount | £362,000 (GBP) |
Funding ID | BB/M012425/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2015 |
End | 01/2016 |
Description | BBSRC EASTBIO Doctoral Training Partnership PhD Studentship |
Amount | £99,000 (GBP) |
Funding ID | BB/J01446X/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2014 |
End | 09/2018 |
Description | BBSRC/Dundee College of Life Sciences (CLS) PhD Studentship |
Amount | £99,000 (GBP) |
Organisation | University of Dundee |
Sector | Academic/University |
Country | United Kingdom |
Start | 09/2013 |
End | 08/2017 |
Description | BBSRC/Dundee College of Life Sciences (CLS) PhD Studentship |
Amount | £24,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2014 |
End | 09/2015 |
Description | CAPES/Dundee PhD Studentship |
Amount | £63,000 (GBP) |
Funding ID | 7148-14-3 |
Organisation | Government of Brazil |
Department | Coordination of Higher Education Personnel Training (CAPES) |
Sector | Public |
Country | Brazil |
Start | 03/2015 |
End | 03/2019 |
Description | Dundee College of Life Sciences (CLS) PhD Studentship |
Amount | £64,000 (GBP) |
Organisation | University of Dundee |
Department | College of Life Sciences |
Sector | Academic/University |
Country | United Kingdom |
Start | 10/2014 |
End | 04/2018 |
Description | EC Horizon 2020 - Marie Sklodowska Curie Individual Fellowship |
Amount | € 183,000 (EUR) |
Funding ID | 655516 Bump-BET |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 10/2015 |
End | 10/2017 |
Description | EC Horizon 2020 - Marie Sklodowska Curie Individual Fellowship |
Amount | € 183,000 (EUR) |
Funding ID | 705705 Anchor E3s |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 08/2016 |
End | 08/2018 |
Description | Foundation BLANCEFLOR Boncompagni-Ludovisi Fellowship |
Amount | 120,000 kr (SEK) |
Organisation | Foundation Blanceflor Boncompagni Ludovisi, née Bildt |
Sector | Academic/University |
Country | Sweden |
Start | 10/2015 |
End | 09/2016 |
Description | MIUR Messaggeri della Conoscenza - Drug Discovery |
Amount | € 40,000 (EUR) |
Funding ID | ID 497 - Drug Discovery |
Organisation | Italian Ministry of Education, Universities and Research |
Sector | Public |
Country | Italy |
Start | 07/2013 |
End | 11/2014 |
Description | Portuguese FCT Studentship |
Amount | € 132,000 (EUR) |
Funding ID | SFRH/BD/101598/2014 |
Organisation | Government of the Portugese Republic |
Department | Foundation of Science and Technology (FCT) |
Sector | Public |
Country | Portugal |
Start | 04/2015 |
End | 04/2019 |
Description | Portuguese FCT Studentship |
Amount | £107,977 (GBP) |
Funding ID | SFRH/BD/92417/2013 |
Organisation | Government of the Portugese Republic |
Department | Foundation of Science and Technology (FCT) |
Sector | Public |
Country | Portugal |
Start | 05/2014 |
End | 05/2018 |
Description | Research collaboration with Boehringer Ingelheim |
Amount | £0 (GBP) |
Organisation | Boehringer Ingelheim |
Sector | Private |
Country | Germany |
Start | 12/2016 |
Description | Wellcome Trust 4 years PhD studentship |
Amount | £151,392 (GBP) |
Funding ID | 102398/Z/13/Z |
Organisation | Wellcome Trust |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 06/2013 |
End | 06/2017 |
Title | chemical biology PROTAC approach to small-molecule induced target protein degradation |
Description | Derivatives of 1-[(cyclopentyl or 2-pyrrolidinyl)carbonylaminomethyl]-4-(1,3-thiazol-5-yl) benzene which are useful for the treatment of proliferative, autoimmune or inflammatory diseases Patent Application No. GB 1521858.9 & GB 1504314.4 (Priority Date: March 13, 2015) PCT HGF Ref. P227094WO / FE (filing date March 14, 2016) WO 2016/146985 (International publication date September 22, 2016) |
Type Of Material | Technology assay or reagent |
Year Produced | 2015 |
Provided To Others? | Yes |
Impact | Paper published in 2014 ACS Chem Biol |
URL | http://www.chemicalprobes.org/mz1 |
Title | chemical genetics bump-and-hole approach to engineer controlled selectivity of BET bromodomain inhibitors |
Description | compounds related to patent Enzyme Function Probes Patent Application No. 1320994.5 & 1401001.1 (Priority Date: 28 Nov 2013) |
Type Of Material | Technology assay or reagent |
Year Produced | 2014 |
Provided To Others? | Yes |
Impact | paper just published in Science impact to see full realization in due course |
URL | http://www.lifesci.dundee.ac.uk/groups/alessio-ciulli/news/just-published-science-our-paper-describi... |
Description | BioNMR collaborative project 261863 proposal no. BIO-NMR-00211 entitled: Structural modelling and dynamics of the Bromodomain Adjacent to Zinc finger domain containing protein 2B bromodomain |
Organisation | Utrecht University |
Country | Netherlands |
Sector | Academic/University |
PI Contribution | Purified proteins to be used in NMR spectroscopic studies and binding assyas, and provided intellectual input |
Collaborator Contribution | Provided access to NMR facility and provided intellectual input and expertise |
Impact | 13. Ferguson, F.M., Dias, D.M., Rodrigues, J.P.G.L.M., Wienk, H., Boelens, R., Bonvin, A.M.J.J., Abell, C., Ciulli, A.* Binding hotspots of BAZ2B bromodomain: histone interaction revealed by solution NMR driven docking. Biochemistry, 2014, 53(42), 6706-6716. |
Start Year | 2013 |
Description | PROTAC collaboration with Boehringer Ingelheim (confidential) |
Organisation | Boehringer Ingelheim |
Country | Germany |
Sector | Private |
PI Contribution | drug discovery research |
Collaborator Contribution | drug discovery research |
Impact | confidential |
Start Year | 2016 |
Title | DERIVATIVES OF 1-[(CYCLOPENTYL OR 2-PYRROLIDINYL)CARBONYLAMINOMETHYL]-4-(1,3-THIAZOL-5-YL) BENZENE WHICH ARE USEFUL FOR THE TREATMENT OF PROLIFERATIVE, AUTOIMMUNE OR INFLAMMATORY DISEASES |
Description | There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, having utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for the preparation thereof, and use in medicine. There is particularly provided PROTACs which bind to a protein within the bromo- and Extra-terminal (BET) family of proteins, and especially to PROTACs including novel small molecule E3 ubiquitin ligase protein binding ligand compounds which selectively induce degradation of the BRD4 protein within the bromodomain of the BET family of proteins. |
IP Reference | WO2016146985 |
Protection | Patent application published |
Year Protection Granted | 2016 |
Licensed | Commercial In Confidence |
Impact | Impact yet to be realised. |
Title | ENZYMES FUNCTIONAL PROBES |
Description | A method of selectively inhibiting a bromodomain in the presence of other bromodomains comprising introducing a functionally silent mutation into the bromodomain in the presence of other wild type bromodomains and selectively inhibiting the mutated bromodomain. |
IP Reference | WO2015079259 |
Protection | Patent application published |
Year Protection Granted | 2015 |
Licensed | Commercial In Confidence |
Impact | impact not yet emerged |
Company Name | AMPHISTA THERAPEUTICS LIMITED |
Description | Amphista Therapeutics is a University of Dundee spin off company that is developing targeted protein degradation platforms |
Year Established | 2017 |
Impact | commercial in confidence |
Description | A kiss of death to drug the 'undruggable' |
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 | Good coverage across the media this morning, the `kiss of death' line has worked well. Attached are cuttings from Daily Express, Herald, The Courier and The National. I've also included below a list of web hits below, which range from the Palestine Telegraph (a site we aren't used to featuring on!) through many of the major news sites including Daily Mail and The Sun, to some of the pharma outlets such as Fierce BioTech and FiercePharma. Cancer breakthrough: Scientists discover how to kill 'undruggable' proteins using 'the kiss of death' (Web) Daily Mail - 14/03/2017 Dundee scientists use 'kiss of death' to target disease (Web) The Scotsman - 14/03/2017 Cancer could be WIPED OUT after scientists discover how to destroy key proteins thought to be 'untouchable' (Web) Angle News - 14/03/2017 A kiss of death to drug the 'undruggable' (Web) EurekAlert - 14/03/2017 A 'KISS OF DEATH' technique could help fight against cancer, says scientists (Web) Express.co.uk - 14/03/2017 Using a 'kiss of death' to neutralize disease-causing proteins (Web) Fierce Biotech - 14/03/2017 Using a 'kiss of death' to neutralize disease-causing proteins (Web) FiercePharma - 14/03/2017 Cancer breakthrough: Scientists kill 'undruggable' protein (Web) NewsReality.com - 14/03/2017 Cancer breakthrough: Scientists discover how to kill 'undruggable' proteins using 'the kiss of death' (Web) Newsrt - 14/03/2017 Dundee scientists use 'kiss of death' to target disease (Web) Newsrt - 14/03/2017 Cancer breakthrough: Scientists kill 'undruggable' protein (Web) One News Page - 14/03/2017 A kiss of death to drug the 'undruggable' (Web) Phys - 14/03/2017 A kiss of death to drug the 'undruggable' (Web) PhysOrg.com - 14/03/2017 A kiss of death to drug the 'undruggable' (Web) ScienceDaily - 14/03/2017 Cancer breakthrough: Scientists kill 'undruggable' protein (Web) Singapore News - 14/03/2017 KISS OF DEATH Cancer could be WIPED OUT after scientists discover how to destroy key proteins thought to be 'untouchable' (Web) The Irish Sun - 14/03/2017 Cancer breakthrough: Scientists discover how to kill 'undruggable' proteins using 'the kiss of death' (Web) The Mail On Sunday - 14/03/2017 KISS OF DEATH Cancer could be WIPED OUT after scientists discover how to destroy key proteins thought to be 'untouchable' (Web) The Scottish Sun - 14/03/2017 KISS OF DEATH Cancer could be WIPED OUT after scientists discover how to destroy key proteins thought to be 'untouchable' (Web) The Sun - 14/03/2017 KISS OF DEATH Cancer could be WIPED OUT after scientists discover how to destroy key proteins thought to be 'untouchable' (Web) The Sun - 14/03/2017 |
Year(s) Of Engagement Activity | 2017 |
URL | http://www.lifesci.dundee.ac.uk/groups/alessio-ciulli//news/our-paper-reporting-first-ternary-crysta... |
Description | Alessio delivers the course Drug Discovery to the Dept. of Pharmaceutical Chemistry at the University of Messina, under the realm of the new MIUR-funded programme Messaggeri della Conoscenza |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Participants in your research and patient groups |
Results and Impact | Taught a course in Drug Discovery which sparked questions, discussions and further interaction. Hosted 4 selected students in my laboratory the following year, and disseminated all activities, also in the form of a video publicly accessible online Students, teachers and public in Italy more aware of the important of exchange programmes between Italy and UK |
Year(s) Of Engagement Activity | 2013 |
URL | http://www.youtube.com/watch?v=GxrQwJO9HB8 |
Description | Media press release: Bump-and-hole approach brings protein breakthrough |
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 | Media press release covering my laboratory recent article published in Science After this press release, I have received a notable number of emails from other colleagues and friends to congratulate us with our achievement but also to tell me that they read the press release and this stimulated their interest in learning more about the topic of epigenetics and small molecule chemical biology and drug discovery. Many individuals have already contacted me to make requests for reagents, and many companies interested in this area have also approached me to express their willingness and interest to collaborate with us. see: http://www.bbsrc.ac.uk/news/health/2014/141020-pr-bump-and-hole-brings-protein-breakthrough.aspx http://www.lifesci.dundee.ac.uk/news/2014/oct/22/ciulli-labs-bump-and-hole-approach-leads-protein-breakthrough |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.bbsrc.ac.uk/news/health/2014/141020-pr-bump-and-hole-brings-protein-breakthrough.aspx |
Description | Participation at the CLS Open Doors Day |
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 | Public/other audiences |
Results and Impact | Our Institute Postdocs, PhD students, Support Staff, Facility Heads and PIs organized the Dundee College of Life Sceinces CLS Open Doors Day with great success on Saturday 8 November. Julianty Juliant, PhD student in my laboratory, participated. We had over 400 people between 10am and 4pm and most of them stayed for over 2 hours. There's been amazing feedback and notes of thanks from members of the public, as well as requests from parent and kids asking us to visit their schools. The most glowing praise was for our scientist/participants:- one lady summarises the main gist of the feedback by saying she found "the scientists just wonderful in their enthusiasm and explanations of the research they are conducting." |
Year(s) Of Engagement Activity | 2014 |
URL | http://www.lifesci.dundee.ac.uk/news/2014/nov/10/well-done-and-thank-you-everyone-who-participated-o... |
Description | Scientists discover 'kiss of death' for cancer-causing proteins |
Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Following on from an interview with Jenny Rodriguez at Global News in Canada, the report went online and included a nice video describing our discovery. http://globalnews.ca/news/3309344/scientist-discover-kiss-of-death-for-cancer-causing-proteins/ |
Year(s) Of Engagement Activity | 2017 |
URL | http://globalnews.ca/news/3309344/scientist-discover-kiss-of-death-for-cancer-causing-proteins/ |