The Epigenetic Control of Gene Expression in Leukaemia and Haematopoiesis

Lead Research Organisation: University of Oxford

Abstract

There are many specialized cells in our body designed to carry out different specific tasks, and yet they all contain the same genetic information. During development, cells receive information that they translate into specific developmental outputs, usually without altering their DNA sequence. Changes in cell phenotype that do not alter the DNA sequence are referred to as “epigenetic”. Human diseases such as cancer often result from changes in gene expression patterns that are not always associated with DNA mutations, thus epigenetic changes are also a key mechanism in human disease. In living cells, genes do not exist as “naked” DNA, but as a highly conserved protein/DNA complex termed chromatin. The basic subunit of chromatin is the nucleosome, which consists of DNA wrapped around an octamer core of globular histone proteins, two each of H2A, H2B, H3, and H4.The N terminal "tails" of these histone proteins are chemically modified with "marks" such as methylation or acetylation. The specific carriers of epigenetic information have not been completely worked out, but emerging work over the past decade has suggested that epigenetic information is established in part by the modification of histone tails. We are specifically interested in how changes in histone methylation lead to transcriptional misregulation in human disease. As a system for asking specific questions about this very complex problem, I work on the Mixed Lineage Leukemia 1 (MLL1) protein, a histone methyltransferase that controls gene activation during development. Mutations in MLL1 also cause aggressive leukaemias in both children and adults. Specific information about MLL1 activity will not only provide potential therapeutic information for this subset of human leukemias, but will also have broader implications for stem cell development and the epigenetic regulation of gene expression in other human diseases.

Technical Summary

The Mixed Lineage Leukaemia 1 protein (MLL1) protein is important for the epigenetic regulation of gene expression during stem and progenitor cell development but is also mutated in a subset of aggressive human leukaemias. The most common leukaemic disruptions of the MLL1 gene are chromosome translocations that fuse the N terminus of MLL1 in frame with over 40 different partner genes creating novel fusion proteins. Recent work has suggested that wild type MLL1 and MLL1 fusion proteins cooperate in leukaemogenesis by together causing aberrant epigenetic profiles at target genes in vivo. Epigenetic changes are often defined as heritable changes in gene expression or chromosome stability that don’t alter the underlying DNA sequence. We are interested in identifying the key molecular events in MLL1 mediated leukaemogenesis in order to fully understand the epigenetic basis for this disease. This major goal has been divided into three key questions: 1) What key downstream gene targets are essential for MLL1 mediated leukaemogenesis?; 2) how do MLL1 and MLL1 fusion proteins control epigenetic gene regulation on a molecular level?; and 3) how are MLL1 and MLL1 fusion proteins recruited to important gene targets in the cell? To answer these questions, we are using xenograft transplant assays to identify Leukaemic Stem Cells (LSCs) in MLL1 patient samples, ChIP-seq to identify and characterise direct gene targets in specific haematopoietic cell populations, small molecular inhibitors and siRNA combined with ChIP and ChIP-seq to determine how MLL1 fusion proteins regulate gene targets in the cell and MLL1 domain analysis coupled with genome wide techniques to determine how MLL1 is recruited to gene targets in the cell. Answering these questions may not only be useful for future therapeutic strategies, but will also inform our basic understanding of epigenetic gene regulation during normal stem and progenitor cell development.

Publications

10 25 50
 
Description Participated in scoping meeting on MRC basic research careers Sept 25, 2013
Geographic Reach National 
Policy Influence Type Membership of a guideline committee
Impact In the interest of nurturing basic research careers to produce the next generation of world class researchers, the MRC Training and Careers Group and the MRC Human Resources team initiated a scoping meeting to discuss the basic research career structures in the MRC. I was part of the scoping meeting and the advice from the subgroup was collated and summarized and distributed to the scoping meeting members. This information provided some initial guidance for the review process that eventually resulted in publication of the document "An MRC review of Next Destinations" and the removal of time-after-the-PhD limits from MRC fellowship applications.
URL https://www.mrc.ac.uk/news/browse/signposting-medical-research-career-options/
 
Description project grants for research into childhood cancer
Amount £48,104 (GBP)
Organisation Children with Cancer UK 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2013 
End 01/2014
 
Title Capture C in t(4;11) leukaemia cells 
Description We performed a novel technique termed Capture C in leukaemia cells to help identify enhancer-promoter interactions at important oncogenes. 
Type Of Material Database/Collection of data 
Year Produced 2016 
Provided To Others? Yes  
Impact We provided a publicly available dataset through GEO that can aid in research by other scientists. In addition, the work generated by this dataset led to an open access publication (see DOI). 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE85988
 
Title ChIPseq in MLL-AF6 leukemia cells 
Description ChIPseq for various chromatin proteins and epigenetic marks in MLL-AF6 leukemia cells, an incurable acute myeloid leukemia 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact A paper is published at Nature communications and is available open access. 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi
 
Title Epigenetic ChIP sequencing dataset in the RS4;11 t(4;11) leukaemia cell line 
Description ChIP-sequencing for multiple epigenetic proteins and histone marks in an RS4;11 t(4;11) leukaemia cell line. 
Type Of Material Database/Collection of data 
Year Produced 2012 
Provided To Others? Yes  
Impact The generation of this dataset allowed us to find a unique correlation between the RUNX1 transcription factor and a specific set of epigenetic marks in a subset of aggressive childhood leukaemias. This led to the publication of a paper in Cell Reports in 2013. In addition, the datset is freely available to the field and will aid in genomic analysis performed by other labs that are interested in epigenetics and leukaemia. 
URL http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE38403
 
Title Epigenetic ChIP sequencing dataset in the SEM t(4;11) leukaemia cell line 
Description We've provided an extensive ChIP-sequencing dataset in a publicly available repository (the Gene Expression Omnibus, GEO) that includes multiple epigenetic marks and chromatin proteins in a t(4;11) leukaemia cell line. 
Type Of Material Database/Collection of data 
Year Produced 2015 
Provided To Others? Yes  
Impact The generation of this dataset has allowed us to predict specific drug combinations, inlcuing the use of a novel epigenetic drug, that might help cure this subset of aggressive childhood leukaemias. In collaboration with another lab at MD Anderson in Texas, this work led to the publication of a paper in 2015 in Cell Reports that showed specific drug combinations can stop the leukaemia from growing. In addition, the datset is freely available to the field and will aid in genomic analysis performed by other labs that are interested in epigenetics and leukaemia. 
URL http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE74812
 
Title Epigenetic ChIP sequencing in normal and patient leukemia cells 
Description It is a collection of different types of epigenomic data (such as ChIP-seq, RNA-seq, ATAC-seq) that have been made publicly available for other researchers to access. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
Impact Generation of these datasets helped publish a paper (see DOI below) that can be used to help predict useful drug combinations for a subset of aggressive leukaemias. In addition, these datasets are available for other scientists to aid in their research. 
URL https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE83671
 
Title Transcription factor ChIP sequencing dataset in the RS4;11 t(4;11) leukaemia cell line 
Description We've provided an extensive ChIP-sequencing dataset in a publicly available repository (the Gene Expression Omnibus, GEO) that includes multiple transcription factors in a t(4;11) leukaemia cell line. 
Type Of Material Database/Collection of data 
Year Produced 2013 
Provided To Others? Yes  
Impact The generation of this dataset allowed us to find a unique correlation between the RUNX1 transcription factor and a specific set of epigenetic marks in a subset of aggressive childhood leukaemias. This led to the publication of a paper in Cell Reports in 2013. In addition, the datset is freely available to the field and will aid in genomic analysis performed by other labs that are interested in epigenetics and leukaemia. 
URL http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE42075
 
Description BCL-2 and epigenetic inhibitors in MLL-AF4 leukaemias 
Organisation University of Texas
Department M. D. Anderson Cancer Center
Country United States 
Sector Academic/University 
PI Contribution t(4;11) translocations preoduce rare but highly aggressive leukemias in infants, children and adults. We performed an extensive molecular analysis that showed that this mutation directly results in the upregulation of a gene target named BCL-2 that results in a suppression of apoptosis. Our molecular analysis also provided a rationale for using different specific drug combinations to0 combat these leukemias.
Collaborator Contribution Our collaborators at MD Anderson in Texas were able to use a newly developed drug to BCL-2 to show that this drug could stop leukemia growth in model systems. This provides a rationale for moving forward with this drug in clinical trials. Further, using our molecualr analysis as a foundation, they have started testing the effect of BCL-2 inhibitors in combination with other epigenetic drugs.
Impact This collaboration has resulted in the publication of a paper in Cell Reports in 2015: Benito et al ... Milne TA, Konopleva M. MLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199. Cell Rep. 2015 Dec 29;13(12):2715-27. doi: 10.1016/j.celrep.2015.12.003. PubMed PMID: 26711339;
Start Year 2014
 
Description ChIP sequencing in acute leukemias 
Organisation University of California, San Francisco
Department School of Medicine (UCSF)
Country United States 
Sector Academic/University 
PI Contribution Providing ChIP sequencing datasets in patient samples for BCL6, E2A-PBX and MLL-AF4.
Collaborator Contribution Dr. Huimin Geng performed bioinformatics analysis of ChIPseq data, Dr. Markus Muschen's lab provided patient samples and performed pre clinical studies on acute leukaemias
Impact This work has resulted in the publication of several papers: 1: Geng H, Brennan S, Milne TA, Chen WY, Li Y, Hurtz C, Kweon SM, Zickl L, Shojaee S, Neuberg D, Huang C, Biswas D, Xin Y, Racevskis J, Ketterling RP, Luger SM, Lazarus H, Tallman MS, Rowe JM, Litzow MR, Guzman ML, Allis CD, Roeder RG, Müschen M, Paietta E, Elemento O, Melnick AM. Integrative epigenomic analysis identifies biomarkers and therapeutic targets in adult B-acute lymphoblastic leukemia. Cancer Discov. 2012 Nov;2(11):1004-23. doi: 10.1158/2159-8290.CD-12-0208. Epub 2012 Oct 29. PubMed PMID: 23107779; 2: Wilkinson AC, Ballabio E, Geng H, North P, Tapia M, Kerry J, Biswas D, Roeder RG, Allis CD, Melnick A, de Bruijn MF, Milne TA. RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell Rep. 2013 Jan 31;3(1):116-27. doi: 10.1016/j.celrep.2012.12.016. Epub 2013 Jan 24. PubMed PMID: 23352661; 3: Geng H, Hurtz C, Lenz KB, Chen Z, Baumjohann D, Thompson S, Goloviznina NA, Chen WY, Huan J, LaTocha D, Ballabio E, Xiao G, Lee JW, Deucher A, Qi Z, Park E, Huang C, Nahar R, Kweon SM, Shojaee S, Chan LN, Yu J, Kornblau SM, Bijl JJ, Ye BH, Ansel KM, Paietta E, Melnick A, Hunger SP, Kurre P, Tyner JW, Loh ML, Roeder RG, Druker BJ, Burger JA, Milne TA, Chang BH, Müschen M. Self-enforcing feedback activation between BCL6 and pre-B cell receptor signaling defines a distinct subtype of acute lymphoblastic leukemia. Cancer Cell. 2015 Mar 9;27(3):409-25. doi: 10.1016/j.ccell.2015.02.003. PubMed PMID: 25759025;
Start Year 2010
 
Description Developing a model of Infant MLL-AF4 leukemia 
Organisation University of Oxford
Department Radcliffe Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We are collaborating with the labs of Dr. Irene Roberts and Dr. Anindita Roy. We are providing help and expertise on designing contructs to express the MLL-AF4 infant leukaemia protein
Collaborator Contribution Our collaborators are providing expertise on human B cell development and on targeting the correct cell type to produce a model for this aggressive infant leukaemia.
Impact No outputs yet
Start Year 2015
 
Description Epigenetic inhibitors in MLL-AF4 leukaemias I 
Organisation Mount Sinai Hospital (USA)
Country United States 
Sector Hospitals 
PI Contribution We are providing ChIPseq and bioinformatic analysis of leukaemia cells
Collaborator Contribution Dr Jian JIn's lab at Mount Sinai in the US are synthesizing large amounts of compounds for preclinical work and molecular analysis. The Newcastle lab of Prof Olaf Heidenreich are conducting xenograft transplant analysis of leukaemias and the effect of specific inhibitors that control the activity of a class of epigenetic repressor proteins termed the PRC complex. These novel inhibitors are also being tested in combination with Dexamethasome, a commonly used chemotherapeutic agent.
Impact None yet
Start Year 2014
 
Description Epigenetic inhibitors in MLL-AF4 leukaemias I 
Organisation Newcastle University
Department Northern Institute for Cancer Research Newcastle
Country United Kingdom 
Sector Academic/University 
PI Contribution We are providing ChIPseq and bioinformatic analysis of leukaemia cells
Collaborator Contribution Dr Jian JIn's lab at Mount Sinai in the US are synthesizing large amounts of compounds for preclinical work and molecular analysis. The Newcastle lab of Prof Olaf Heidenreich are conducting xenograft transplant analysis of leukaemias and the effect of specific inhibitors that control the activity of a class of epigenetic repressor proteins termed the PRC complex. These novel inhibitors are also being tested in combination with Dexamethasome, a commonly used chemotherapeutic agent.
Impact None yet
Start Year 2014
 
Description Gene tuning 
Organisation University of Oxford
Country United Kingdom 
Sector Academic/University 
PI Contribution We contributed expertise and ran a number of collaborative experiments with the Fulga lab
Collaborator Contribution The Fulga lab contributed expertise and ran a number of collaborative experiments with us.
Impact There is a current publication that resulted directly from this work (Michaels et al Nat Comm, 2019 PMID: 30778069), a second publication in preparation and a published patent (Pub. No.: WO/2018/011590 International Application No.: PCT/GB2017/052068, see also patent section)
Start Year 2015
 
Description Inhibition of epigenetic proteins in leukemia 
Organisation University of Oxford
Department Structural Genomics Consortium (SGC)
Country United Kingdom 
Sector Public 
PI Contribution Testing inhibitors for their effect on leukemic cell growth
Collaborator Contribution The SGC at the University of Toronto has provided several high quality inhibitors for methyltransferases and demethylases.The SGC at the University of Oxford has provided several high quality inhibitors for bromodomain containing proteins
Impact None yet, but we expect to publish some papers soon.
Start Year 2012
 
Description Inhibition of epigenetic proteins in leukemia 
Organisation University of Toronto
Department Strcutural Genomics Consortium
Country Canada 
Sector Academic/University 
PI Contribution Testing inhibitors for their effect on leukemic cell growth
Collaborator Contribution The SGC at the University of Toronto has provided several high quality inhibitors for methyltransferases and demethylases.The SGC at the University of Oxford has provided several high quality inhibitors for bromodomain containing proteins
Impact None yet, but we expect to publish some papers soon.
Start Year 2012
 
Description RUNX1 in leukemia 
Organisation University of Oxford
Department Radcliffe Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We initiated an analysis on the role of RUNX1 in MLL leukemias.
Collaborator Contribution The lab of Dr. Marella De Bruijn has provided us with reagents and expert advice.
Impact We have published a 2013 paper together in the the journal Cell Reports: Wilkinson AC, Ballabio E, Geng H, North P, Tapia M, Kerry J, Biswas D, Roeder RG, Allis CD, Melnick A, de Bruijn MF, Milne TA. RUNX1 is a key target in t(4;11) leukemias that contributes to gene activation through an AF4-MLL complex interaction. Cell Rep. 2013 Jan 31;3(1):116-27. PubMed PMID: 23352661
Start Year 2012
 
Description SMYD2 inhibitors in leukaemias 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution We are testing SMYD2 inhibitors on the growth of leukaemia cells and trying to understand the molecular mechanisms underlying SMYD2 function.
Collaborator Contribution Astra Zeneca have provided large quantities of a novel and specific compound that inhibits the activity of the SMYD2 methyltransferase.
Impact None yet.
Start Year 2012
 
Description The role of RUNX2 in MLL-AF9 acute myeloid leukaemia 
Organisation University of Oxford
Department Radcliffe Department of Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We are analyzing the role of RUNX2 in acute myeloid leukaemias.
Collaborator Contribution Prof Paresh Vyas and I are jointly supervising a student and directing the goals of the project.
Impact None yet.
Start Year 2014
 
Description microRNA repression of cancer cells 
Organisation University of Oxford
Department Weatherall Institute of Molecular Medicine (WIMM)
Country United Kingdom 
Sector Academic/University 
PI Contribution We are providing cell lines and expertise on the mechanisms of leukaemia. In collaboration with Dr. Tudor Fulga, we are together directing a project that explores the role of micro RNAS in poor prognosis human leukaemia with an eventual hope this could be of therapeutic use.
Collaborator Contribution The lab of Dr. Tudor Fulga at the WIMM is providing expertise and tools for analyzing micro RNAs.
Impact None yet
Start Year 2014
 
Title METHOD FOR MODIFYING GENES 
Description The present invention relates to method of modulating the level of expression of an endogenous gene in a cell, the method comprising inserting a heterologous microRNA (miRNA) response element (MRE) into the 3'-untranslated region (3'-UTR) of the gene. The binding of endogenous miRNAs to the MRE results in or leads to a repression of the level of expression of the gene. The invention also relates to cells and transgenic animals whose endogenous genes comprise heterologous MRE in their 3'-UTRs. 
IP Reference WO2018011590 
Protection Patent application published
Year Protection Granted 2018
Licensed No
Impact Publication of a paper in Nature Communications. Other patents applied for: US Patent Application no. 16/636,764 Project 13338, Project Title:- MicroRNA checkpoint inhibitor
 
Company Name OxStem Oncology 
Description There is a pressing need to develop therapeutics which can target stem cells. OxStem Ltd is an investment company (http://www.oxstem.co.uk/, £16.9M invested in the startup) to fund a series of spinouts ("stem companies") at Oxford. The first such stem company is OxStem Oncology (OSO), a subsidiary company of OxStem Ltd. OxStem Oncology aims to identify a new class of drugs that will differentiate 'cancer stem-like cells' (CSLCs) to more benign states that will improve clinical outcomes and overcome resistance/relapse. 
Year Established 2016 
Impact This spin out has attracted investment from the US (via OxStem Ltd) and is in the process of attracting additional international investment. It has generated full time scientific posts for more than 10 people in the UK so far. OxStem are delighted to be featured in the May 2017 issue of Nature in an article entitled "Masters of Medicine". OxStem was selected as one of six innovative and disruptive University start-up biotechnology companies from around the world to be profiled in the article.
Website http://www.oxstem.co.uk/product-pipeline/oncology
 
Description Annual Molecular Haemopoiesis conference 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact I helped plan and organize the annual Molecular Haemopoiesis conference number 17 (2014) and 18 (2015).

The Molecular Haemopoiesis conference attracts researchers from all over the UK and Europe and also a few from North America. The specific impact it has is that it is an excellent opportunity for researchers to mix and exchange ideas and the meeting is effective at raising the intellectual capital of UK science as well as raising the profile of UK science within the international community. Directly due to these and past Molecualr Haematology meetings I have personally sopken to individual inter
Year(s) Of Engagement Activity 2014,2015
 
Description Athena Swan UCL Career Day Event 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact The target audience consisted of about 30-50 early career scientists, graduate students and postgraduates on April 10th, 2014. I was the first of 6 speakers for a UCL Cancer Institute Athena Swan Week Career Talks Day. I mainly gave a talk on my own career path and I included advice and hints on how to make career choices in science. I also gave practical advice on several different areas such as how to build a competitive CV, looking for and applying for jobs, preparing for an interview and presenting a job talk.

The engagement included many individual questions after the talk during the lunch and coffee breaks covering a wide range of topics including work/life balance, applying for jobs in academia as well as applying for jobs in industry. I also received several follow up emails from people asking for specific advice about CV's and interviews.
Year(s) Of Engagement Activity 2014
URL http://www.ucl.ac.uk/cancer/athenaswan/swanci
 
Description Career talk to students and postdocs at the Weatherall Institute of Molecular Medicine 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact The career talk stimulated much discussion afterwards about careers in science and resulted in the formation of a postdoc association at the WIMM. The postdoc association are engaged in different issues involving postdocs and PhD students and career planning.

After my talk, several postdocs approached me and directly suggested the formation of the postdoc association.
Year(s) Of Engagement Activity 2013
 
Description Children with Cancer UK 25th anniversary celebration 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Supporters
Results and Impact I presented a poster at this event designed as an outreach from the charity Children with Cancer UK to members of parliament and to members of the general public who had contributed to the charity. I mainly talked about my work and the impact of basic research on disease with members of the general public who came to my poster. I also talked to some of the other organisers and guests of the event and I emphasised how their funding has helped my research and how this might one day hopefully impact treating children with leukaemia. I also talked to other scientists at the event about their research.

In this case I think the strongest impact was on my own perspective. I talked to a few different couples who were contributors to the charity and had lost children to leukaemia. These interactions have brought me more focus in my own research.
Year(s) Of Engagement Activity 2013
URL http://www.childrenwithcancer.org.uk/News/celebrating-science-2013
 
Description Epigenetic drug targeting talk at the Royal Berkshire Hospital in Reading 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Health professionals
Results and Impact My talk was geared towards the audience which consisted of consultants, associate specialists and 2 trainee haematology registrars (Oxford rotation) as well as specialist nurses, and clinical trials nurses. The talk was designed to show how basic research in epigenetics could lead to drug design that could eventually be used in the clinic.

The engagement included many individual questions after the talk during the lunch and included interesting comments from clinicians about the potential practicality of different drug designs.
Year(s) Of Engagement Activity 2014
 
Description Hosted 2 A-Level students for a week long work experience placement 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Talked and hosted 2 A-Level students for a week long work experience placement
Year(s) Of Engagement Activity 2016
 
Description Oxford chromatin and transcription meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation keynote/invited speaker
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Talk initiated interactions and discussion with fellow scientists at Oxford across departments that don't normally have any contact.

All the transcription researchers at Oxford became much more aware of each others research thus increasing the possibility for local collaborations.
Year(s) Of Engagement Activity 2015
 
Description Summer Internship 
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 Undergraduate students
Results and Impact An undergraduate student had an internship in the lab for several weeks in the summer in order to learn more about how science works and how research is conducted.

After his internship, the student expressed a strong interest in one day becoming a scientist himself.
Year(s) Of Engagement Activity 2014
 
Description Talk at ChemBio Hub Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Industry/Business
Results and Impact The target audience consisted of members of industry, chemists, drug developers, members of the Structural Genomics Consortium (SGC) and basic researchers. The purpose of the meeting was to bring together people Oxford-wide who were interested in drug development.

Several collaborations were established and contacts between industry and academics were strengthened.
Year(s) Of Engagement Activity 2014
URL https://chembiohub.ox.ac.uk/symposium2014/
 
Description Talk at the Annual Oxford Developmental Biology Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact The talk presented a leukaemia perspective to a developmental biology crowd. The talk stimulated several questions and discussions afterwards.

There were discussions with colleagues about the relationship between development and leukaemia.
Year(s) Of Engagement Activity 2014
 
Description Talk in Leuven 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact A scientific talk at the Department of Pharmaceutical and Pharmacological Sciences, UZ St. Rafael, Leuven, Belgium that stimulated questions from the audience.

After my talk, we discussed applying for joint funding for an ERC grant.
Year(s) Of Engagement Activity 2014
 
Description University of Edinburgh, MRC Centre for Regenerative Medicine talk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact The talk stimulated many questions and discussion afterwards.

The most important impact was that the talk caused a collaboration to form between my lab and another lab at the institute.
Year(s) Of Engagement Activity 2014
 
Description University of Oxford International Careers Day 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Local
Primary Audience Postgraduate students
Results and Impact I was a member of an International Academia (Science) panel consisting of myself and three other international scientists, on Jan 25,2014 at the University of Oxford exam schools. We were all asked to talk for about 10 minutes on our experiences to date, how we got into our roles, the opportunities and challenges we have faced, and then we offered tips for students interested in similar / parallel roles and academic careers.

After our brief talks, we fielded several questions from the audience (about 20 people) asking for specific advice on an international career in science (ex moving countries and working in other countries).
Year(s) Of Engagement Activity 2014
URL http://www.careers.ox.ac.uk/international-careers-day-january-25th-2014/