Targeting etiologic molecular mechanisms to treat human diabetes

Lead Research Organisation: Imperial College London
Department Name: Metabolism, Digestion and Reproduction

Abstract

One of the major goals of modern medicine is to develop more efficient personalized therapies for diseases that impose a heavy burden on our society, including debilitating chronic diseases such as diabetes mellitus. The drugs that are currently used to treat diabetes do not aim to correct the molecular causes of the disease but simply aim to lower blood sugar, and therefore do not prevent disease progression. The most common form of this disease is known as Type 2 diabetes. Recent genetic studies have pinpointed to candidate genetic factors that predispose to this form of diabetes. This promises to facilitate the development of treatments that target specific genes that are truly involved in the disease mechanisms. Such treatments can theoretically be more efficient for individuals in whom diabetes is shown to be caused by those particular mechanisms. In this project we have set out to discover novel therapies that target the molecular mechanism in patients who develop diabetes due to mutations in a gene named HNF1A. This defect is the most common form of diabetes in which the genetic derangement is unequivocally established, although it is rare compared to the overall frequency of Type 2 diabetes. Nonetheless, there is evidence indicating that some genetic factors associated to HNF1A might also affect the risk to develop more common classic forms of Type 2 diabetes. Because the genetic defect in HNF1A diabetes is clear, it provides an ideal test bed to develop therapies that target genetic factors in diabetes. We will use a combination of chemical and genomic approaches to identify candidate compounds to treat HNF1A diabetes, and also to unravel the mechanisms that mediate their beneficial effects. We will also create new models of HNF1A-deficient diabetes for testing and developing new drugs. This programme is therefore designed to deliver novel candidate therapies for people with mutations in the HNF1A gene, and theoretically for a subset of individuals with Type 2 diabetes that have genetic risk factors associated with this same gene. The therapies that we propose to develop have the potential to be rapidly translated into the clinic. These drugs can impact the underlying causes and thereby modify the progression of disease.

Technical Summary

One of the major goals of modern medicine is to develop more efficient personalized therapies to treat chronic diseases that impose a heavy burden on our society. Recent progress in our understanding of the genetic predisposition of Type 2 diabetes promises to facilitate personalized therapies that target the molecular mechanisms that underlie this disease. We have set out to discover novel therapies that target the molecular mechanism in patients who develop early-onset diabetes to heterozygous mutations in the gene encoding the transcription factor HNF1A. This genetic defect represents the most common known form of Mendelian diabetes. Although it is rare compared to classic late-onset Type 2 diabetes, sequence variants near HNF1A predispose to late-onset disease, suggesting that different variants in the same locus might lead to different forms of diabetes. HNF1A-deficient diabetes is of interest to us because it has a clearly recognizable molecular defect. In the current proposal we plan to develop novel therapies that target this molecular defect. We will use an integrative chemical and genomic approach that is designed to uncover the molecular mechanisms that mediate the beneficial effects of novel therapies. We will also create new genetic models of HNF1A-deficient diabetes for in vivo drug testing and development. In conclusion, this programme is expected to deliver candidate targeted therapeutics for patients with highly penetrant mutations in HNF1A, and possibly for individuals that harbor Type 2 diabetes risk variants in the HNF1A locus. Such therapies have the potential for rapid translation into the clinic, and unlike current drugs that simply modify glycemia, they can impact the underlying pathogenic defects and thereby modify the progression of disease.

Planned Impact

The primary beneficiaries of the research proposed here should be the general public, the UK Pharmaceutical industry, and the Scientific community.

1. UK healthcare. Type 2 diabetes affects ~3m UK subjects and ~30m Europeans. These values are predicted to grow further in an "epidemic" driven by increasingly sedentary lifestyles and obesity. The disease is a major cause of stroke, blindness, amputations painful neuropathy, renal failure, cardiovascular disease and is now also associated to increased risk of cancer. The high prevalence of diabetes was recently predicted to contribute to a lowered overall life expectancy in the UK for the first time in 200 years. The direct economic costs account for 7-13 % of health care costs in most developed societies (IDF Diabetes Atlas, 2003) and are further aggravated by increased absenteeism and decreased individual productivity.
One of the major goals of modern medicine is to develop personalized medicines. It is widely accepted that Type 2 diabetes is a heterogeneous disorder, and therefore different patients are expected to respond differently to diverse therapies. A small proportion of patients diagnosed with Type 2 diabetes have severe defects in the HNF1A gene, whereas many others have sequence variants near this gene, potentially regulating HNF1A, which increase the risk for developing Type 2 diabetes. This project seeks to identify therapies that specifically ameliorate diabetes in those individuals in which HNF1A plays a role in the development of the disease. Furthermore, because the treatment does not simply ameliorate blood sugar, but actual targets the molecular cause, it has the potential to block the progression of the disease. This could have significant impact on the requirement of further medications such as insulin, and most importantly may impact chronic complications that are a major burden for western healthcare systems.

2. The UK Pharmaceutical Industry. The global market for anti-diabetes drugs is estimated to be worth ~$30 billion. Following its joint Workshop with the Association of British Pharmaceutical Industries (ABPI) in March 2011, the MRC concluded that pancreatic beta cell biology should become a Strategic Priority, alongside Stratified Medicine. The present application addresses both of these areas. New drug targets and leads are desperately needed for the Pharmaceutical industry to produce novel approaches to diabetes treatment. By addressing a target that is unequivocally important for human beta cells, the proposed study will enhance feeds of new Intellectual Property to this sector.
Numerous pharmaceutical companies have a specific interest in the development of novel types of therapies diabetes. The PIs are members of two trans-European diabetes academic and industrial partnerships named "DIRECT" http://www.direct-diabetes.org/ (JF) and "IMIDIA" (http://www.imidia.org/) (GR). The PIs therefore have excellent continued access to UK and Europe-based companies and plan to approach them to exploit the findings for the development of new diabetes therapies.

3. The scientific community. This programme aims to demonstrate the utility of a therapeutic strategy that has potential ramifications for the treatment of human haploinsufficient conditions beyond diabetes. It will also generate knowledge on central regulatory mechanisms in pancreatic beta cells, and provide a broad range of chemical and genetic research tools that should accelerate research in the islet research field. Collaborative interactions with clinical diabetes investigators will help advance clinical science in UK. Finally, the programme will have a significant training component. Each of the research fellows directly involved in the project will enhance their professional skills with training in basic biomedical research and thus their develop their skill set for application in both the academic and commercial sectors.

Publications

10 25 50
 
Description ChroMe H2020
Amount € 251,688 (EUR)
Funding ID 675610-ChroMe-H2020-MSCA-ITN-2015 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 03/2016 
End 02/2020
 
Description ERC - DecodeDiabetes - Expanding the genetic etiological and diagnostic spectrum of diabetes mellitus
Amount € 2,243,746 (EUR)
Funding ID 789055 
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start  
 
Description Genetic and nutritional control of pancreatic beta cell identity.
Amount £2,070,355 (GBP)
Funding ID MR/R022259/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2018 
End 07/2023
 
Title CRISPR/Cas9 tools for genome engineering 
Description Plasmids for genome/epigenome editing: These plasmid collection contains new backbones for CRISPR/Cas9 editing, which can be deployed to investigate genomic loci in human pancreatic beta cells by either deletion of specific DNA sequences, CRISPR-mediated repression or CRISPR-mediated activation. In addition, we also provide a series of lentiviral vectors that we used in previous analyses of diabetes-associated loci, containing guide RNAs against diabetes susceptibility genes and enhancers. 
Type Of Material Technology assay or reagent 
Year Produced 2015 
Provided To Others? Yes  
Impact These reagents have had more than 500 requests by investigators worldwide, most of which can be documented in the Addgene website. They are published in several publications (Miguel Escalada, Nature Genetics 2018, Cebola Nature Cell Biology 2015, Pasquali Nat Genet 2014) and are available to the research community via Addgene (https://www.addgene.org/Jorge_Ferrer/) We have also shared vectors with a number of laboratories through direct interactions (e.g. Rhodes et al., Lancet Resp Medicine 2018). 
URL https://www.addgene.org/Jorge_Ferrer/
 
Title Cloning protocol for dual sgRNA CRISPR/Cas9 targeting: 
Description Cloning protocol for dual sgRNA CRISPR/Cas9 targeting, published in Protocol Exchange as well as Miguel Escalada et al, Nat Genet 2019, accompanied by deposit of plasmids in Addgene (see ee Addgene entry in Research Tools & Methods for more information on the plasmids) 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact authors have recieved numerous emails, and a high number of requests of plasmids needed to carry out this method, most of them through Addgene (see Addgene entry in Research Tools & Methods for more information on the plasmids) 
URL https://protocolexchange.researchsquare.com/article/nprot-7395/v1
 
Title Conditional mouse allele for cell-specific inactivation of a lncRNA gene in pancreas, liver, gut, beta cells, glucagon cells (Hnf1a LoxP/LoxP + cell-specific Cre) 
Description A loxP conditional allele to delete a long noncoding RNA (HASTER) that regulates HNF1A. KO for this gene causes diabetes in mice, and the mechanisms operate in human beta cells 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2016 
Provided To Others? No  
Impact This model has revealed a new function for long noncoding RNAs, and shows that mutations of a long noncoding RNA cause diabetes. It has been submitted for publication 
 
Title Generation mouse knock-in models for cell-specific conditional deletion in mice 
Description Ins1Cre - Cre recombinase is expressed in insulin-producing beta cells of the pancreas. Ins1CreER - Cre-ERT2 is expressed in insulin-producing beta cells of the pancreas. This model is useful for applications requiring tamoxifen-induced deletion of floxed sequences in beta cells. Available from JAX 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2016 
Provided To Others? Yes  
Impact The Ins1Cre model is useful for applications requiring deletion of floxed sequences in beta cells. It is widely used in the diabetes research community, as it has been cited more than 120 times (Google Scholar) Diabetologia 2015 Mar;58(3):558-65. doi: 10.1007/s00125-014-3468-5 
 
Title Hnf1a LoxP mouse allele to study HNF1A-deficient diabetes 
Description Conditional mouse allele for cell-specific inactivation of the Hnf1a gene in pancreas, liver, gut, beta cells, glucagon cells (Hnf1a LoxP/LoxP + cell-specific Cre) HNF1A is mutated in rare forms of diabetes, and carries variants that increase risk for type 2 diabetes 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2020 
Provided To Others? Yes  
Impact This has already resulted in a publication, based on an unexpected finding that HNF1A is a tumor supressor The major findings from this study pertaining to diabetes are being prepared for 2 initial manuscripts. 
 
Title Knock-in reporter line to perform screens for gene regulators in human beta cells 
Description Knock-in reporter line to perform screens for regulators of the endogenous HNF1A gene in human beta cells 
Type Of Material Cell line 
Year Produced 2016 
Provided To Others? No  
Impact Work in progress, and will be made available to the community when it is published. or before that through collaborations 
 
Title Mouse knock-in mutation to study a human mutation causing monogenic diabetes 
Description Mouse knock-in mutation to study a human mutation in HNF1A that unlike any other HNF1A mutation only causes diabetes in homozigosity. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2016 
Provided To Others? No  
Impact This model is still under investigation. It is a valid model for testing drugs for HNF1A-deficient islet dysfunction 
 
Title Mouse model to study a human mutation that causes neonatal diabetes 
Description HIP mice have been created to study a human mutation in the INS regulatory region causing neonatal diabetes Akerman et al, Cell Reports, 2021 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2021 
Provided To Others? Yes  
Impact Recently made available and published, hence impact on the field is difficult to assess 
 
Title Generation and public release of human genomic and epigenomic annotations and datasets 
Description - Annotations of human pancreatic islet long non-coding RNAs and associated datasets - Annotations of regulatory elements in human embryonic pancreas and associated datasets - Annotations of regulatory elements in human pancreatic islets and associated datasets - Annotations of 3D chromatin interactions in human pancreatic islets and associated datasets These datasets are publically available in a variety of formats and locations for access: 1. -3D chromatin maps in human pancreatic islets as well as refined regulatory annotations (Miguel-Escalada et al, Human pancreatic 3D chromatin architecture provides insights into the genetics of type 2 diabetes. Nature Genetics 2019). EGA datasets: https://ega-archive.org/studies/EGAS00001002917. Contains the following datasets: 13 ATAC-Seq datasets, 6 ChIP-Seq datasets of Mediator, 3 ChIP-Seq datasets of Cohesin, 14 ChIP-Seq datasets of H3K27ac of islets cultured in 11mM glucose, 7 ChIP-Seq datasets of H3K27ac of islets cultured in 4mM glucose, 4 Promoter Capture HiC datasets, 14 RNA-Seq datasets (7 datasets from human islets cultured in 11mM glucose and 7 from islets cultured in 4 mM glucose) and 2 4C-Seq datasets from human endoC-bH1 cells. -- Data from this study can be visualized in the following browsers: - Islet regulome browser (http://isletregulome.org/isletregulome),  - CHiCP browser (https://www.chicp.org)   - WashU Epigenome browser using this session link: - http://epigenomegateway.wustl.edu/browser/?genome=hg19&session=62hGf7nfcS&statusId=140947077 -- Processed files from this study have been deposited and accessed at: https://www.crg.eu/en/programmes-groups/ferrer-lab#datasets These files include: 1. Refined islet regulome 2. The robust set of ATAC-Seq peaks in human pancreatic islets 3. Consistent set of Mediator, cohesin, H3K27ac and H3K4me3 ChiP-Seq peaks in human islets 4. List of islet super-enhancers in human islets (defined using ROSE algorithm) 5. ChromHMM segmentation model 6. List of islet TAD-like domains and PATs (Promoter-Associated 3D territories) 7. List of high-confidence pcHiC interactions 2. Data from Weedon et al Nat Genet 2014 & Cebola et al Nat Cell Biol 2015 Raw files of RNAseq ChIP-seq experiments for active histone modifications and key developmental transcription factors in human pancreatic progenitor cells are available at ArrayExpress Archive under accession number E-MTAB-3061 and E-MTAB-1990. Annotations available from supplementary data in manuscripts and Islet regulome browser (http://isletregulome.org/isletregulome),  3. Data from Akerman et al, Cell Metabolism. Human islet lncRNAs RNAseq readsEGAD00001003992 track hubs https://genome-euro.ucsc.edu/cgi-bin/hgHubConnect?hgsid=567406633_nrej3oBtjncMDvjpAJ6YTyGwkWqE&redirect=manual&source=genome.ucsc.edu Islet regulome browser (http://isletregulome.org/isletregulome),  http://www.imperial.ac.uk/medicine/beta-cell-genome-regulation-laboratory/resources/ 4. Data from Pasquali et al Nat Genet 2014: Islet Regulome Browser http://pasqualilab.upf.edu/app/isletregulome (currently managed by Dr Pasquali, but created during his stay in the Ferer lab) ChIP-seq H3K27ac, H3K4me1, PDX1, NKX2.2, NKX6.1, MAFB, FOXA2, CTCF, H2AZ: ArrayExpress under accession E-MTAB-1919 Genomic coordinates of Open chromatin classes: https://static-content.springer.com/esm/art%3A10.1038%2Fng.2870/MediaObjects/41588_2014_BFng2870_MOESM31_ESM.xlsx ChiP-seq processed data: ChiP-seq processed data: Genomic coordinates of TF binding sites https://static-content.springer.com/esm/art%3A10.1038%2Fng.2870/MediaObjects/41588_2014_BFng2870_MOESM34_ESM.xlsx ChiP-seq processed data: Genomic coordinates of enhancer clusters https://static-content.springer.com/esm/art%3A10.1038%2Fng.2870/MediaObjects/41588_2014_BFng2870_MOESM35_ESM.xlsx 
Type Of Material Database/Collection of data 
Year Produced 2014 
Provided To Others? Yes  
Impact Human genomic and epigenomic datasets have been widely used by the genomics, epigenomic and diabetes communities. The manuscripts that have generated them have received collectively more than 2000 citations, but most individuals who use these data (raw data, annotations, browsing in UCSC, regulome, etc browsers) do not necessarily cite a manuscript. The URL below is just one of many, see the box above for other examples 
URL https://ega-archive.org
 
Title Generation of mouse pancreatic and HNF1A-dependent epigenomic and genomic annotations 
Description Genomic and epigenomic data from HNF1A recruits KDM6A to activate differentiated acinar cell programs that suppress pancreatic cancer EMBO J (2020)39:e102808 https://www.embopress.org/doi/full/10.15252/embj.2019102808 See also video https://www.youtube.com/watch?v=FFBi4LZAXDM 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? Yes  
Impact Data has been made available recently, and impact is more difficult to assess. 
URL https://www.ebi.ac.uk/ena/browser/view/PRJEB32478
 
Description ChroMe Marie Sklodowska-Curie Action 
Organisation European Commission
Country European Union (EU) 
Sector Public 
PI Contribution This has been a Marie Sklodowska-Curie Action that trained PhD students. Our team provided expertise in diabetes pathophysiology and treatment, genetics and genomic analysis. We have provided training in network courses and communicated science in the consortiumn meetings and an international conference organized by Chrome. Our team has specifically traing PhD student Berta Font-Conill, who successfully performed (a) chemical screen of HNF1A-dependent regulators, (b) genetic screen of cis-regulatory sequences of the HNF1A locus. The results are pending publishing in two publications, and will be part of her thesis that should be submitted to the College in the next two months
Collaborator Contribution This consortium has train PhD students in various areas of expertise relevant to metabolic disease and epigenetics.
Impact As outlined above, our team provided expertise in diabetes pathophysiology and treatment, genetics and genomic analysis. We have provided training in network courses and communicated science in the consortiumn meetings and an international conference organized by Chrome. Our team has specifically trained PhD student Berta Font-Conill, who successfully performed (a) a high throughput chemical screen of HNF1A-dependent regulators, (b) genetic screen of cis-regulatory sequences of the HNF1A locus. The results are pending publishing in two publications, and will be part of her thesis that should be submitted to the College in the next two months. Berta Font expects to pursue a postdoctoral career in biomedical research in Cambridge, which is the main societal impact of this collaboration.
Start Year 2016
 
Title Candidate therapeutics for diabetes 
Description Chemical and genetic screens were performed to identify target regulators in human beta cells, and have led to studies of candidate therapeutics. 
Type Therapeutic Intervention - Drug
Current Stage Of Development Initial development
Year Development Stage Completed 2020
Development Status On hold
Impact None yet 
 
Title process-specific polygenic risk score for diabetes 
Description A process-specific polygenic risk score was developed and validated in UK biobank to identify individuals who are most likely to be at risk for type 2 diabetes through alterations of beta cell function, rather than other genetic mechanisms of risk. This is a proof of concept genetic risk model that was published in Miguel Escalada et al, Nat Genet 2019, and is being used to develop more advanced models with increased discriminative capacity 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Initial development
Year Development Stage Completed 2019
Development Status On hold
Impact This is a proof of concept genetic risk model that was published in Miguel Escalada et al, Nat Genet 2019, and is being used to develop more advanced models with increased discriminative capacity 
URL https://www.nature.com/articles/s41588-019-0457-0
 
Description 'New Horizons in Genomics ' Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk in an international Genomics scientific conference
Year(s) Of Engagement Activity 2019
URL https://www.engins.org/event/new-horizons-in-genomics-medical-genomics/
 
Description 1st International Symposium for the Consortium for Genetic Studies in Pulmonary Arterial Hypertension, Barcelona, Spain (Keynote Speaker) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This year's venue is aimed to further promote tomorrow's vision of pulmonary vascular disease research and will provide you the latest in clinical care of patients with pulmonary vascular diseases. Several novel features are programmed this year with several debate sessions, abstract based oral sessions, oral presentations awards, rapid ?re poster session and moderated poster discussion to further enrich our learning experience. To further encourage young talent participation, we will be providing a number of Travel Grants in addition to oral presentation awards; rapid ?re awards and poster awards.
Year(s) Of Engagement Activity 2019
 
Description 23rd EASD-Hagedorn Workshop, Keble College, Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact To explore statistical, bioinformatic, and computational methods and tools for analyzing big Omics data in biomedical research, including experimental design for Omics research, next-generation sequencing data analysis, and statistical and bioinformatic methods in high dimensional data. During this course, students will gain practical experience and skills to align RNA-seq reads to reference genome, quantify gene expression, perform differential expression analysis and acquire functional interpretation of results.
Year(s) Of Engagement Activity 2018
 
Description American Diabetes Association Annual Meeting, Orlando, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Scientific Sessions brought together over 14,000 attendees, featuring nearly 900 speakers and more than 2,100 poster presentations, including 47 moderated poster discussions. Social media was buzzing, and there were nearly 300 news reports of breakthroughs presented at Scientific Sessions, with press releases, original news articles and preview coverage of the 78th Scientific Sessions reaching a total potential audience of more than 700 million, putting diabetes front and center in conversations around the globe.The reach of the meeting is impressive, but the real power of Scientific Sessions goes beyond the numbers. The meeting provides unique opportunities for diabetes professionals to make important connections that advance science. The program ranges from large sessions with 6,000 attendees to intimate one-on-one conversations at a poster board. Former colleagues reconnect and new personal and professional connections are made at every corner of the convention center. These are the relationships and exchanges critical to moving progress forward
Year(s) Of Engagement Activity 2018
URL https://professional.diabetes.org/sites/professional.diabetes.org/files/media/78th_scientific_sessio...
 
Description Biotrinity (Europe's leading Biopartnering and Investment conference) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Participated in panel on future of diabetes drug development, Biotrinity (Europe's leading Biopartnering and Investment conference)
Year(s) Of Engagement Activity 2019
URL https://biotrinity.com
 
Description CRC Symposium on Type 2 diabetes and its complications, Cordelier, Paris (Keynote Speaker) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A 2 day symposium on Type 2 diabetes and complications with an important focus on genomic and epigenomic pathways.
Year(s) Of Engagement Activity 2018
 
Description Endocrinology Scientific Sessions, Hospital Clinic de Barcelona 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact later
Year(s) Of Engagement Activity 2018,2019
 
Description F-Tales, Diabetes Brussels, Belgium (Keynote Speaker) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This symposium will focus on beta cell biology, including islet development and normal homeostatic functions, as well as on beta cell replacement strategies such as beta cell replication, directed differentiation of stem cells and reprogramming of differentiated non-beta cells. We will discuss the interaction of grafted beta(-like) cells with signals from multiple organs, including the immune system. The workshop aims to stimulate the interaction between basic science and clinical applications of novel concepts and emerging therapeutic approaches to bring us closer to our ultimate goal: curing patients with diabetes.
Year(s) Of Engagement Activity 2018
 
Description Finnish Diabetes Society Annual Research Meeting in Hanasaari, Keynote Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Genes behind Diabetes discussing beta-cells, monogenic diabetes and SLC30A8 & clinical and genetic subtypes of T2D .
Year(s) Of Engagement Activity 2018
 
Description Imperial Fesitval 
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 Public/other audiences
Results and Impact Participation in an annual Science Fair organized by Imperial College, organized participation by members of the Section who set up a stand
Year(s) Of Engagement Activity 2018
URL http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/eventssummary/event_17-8-2017-12-52-36
 
Description Imperial Great Exhibition Road Science Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Participation in an annual Science Fair organized by Imperial College, organized participation by members of the Section who set up a stand
Year(s) Of Engagement Activity 2017
URL http://www.imperial.ac.uk/festival/
 
Description Imperial Science Festival (later known as Great Exhibition Road Festival) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Participation in an annual Science Fair organized by Imperial College, organized participation by members of the Section who set up a stand

URL is for newer format known as Exhibition Road Festival
Year(s) Of Engagement Activity 2015
URL http://www.imperial.ac.uk/festival/
 
Description Imperial Science Festival (later known as Great Exhibition Road Festival) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Participation in an annual Science Fair organized by Imperial College, organized participation by members of the Section who set up a stand

URL is for newer format known as Exhibition Road Festival
Year(s) Of Engagement Activity 2016
URL http://www.imperial.ac.uk/festival/
 
Description LIMNA Symposium, Lausanne 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited to talk to international meeting organized by Swiss metabolic research community
Year(s) Of Engagement Activity 2019
URL http://www.limna.ch/events/625
 
Description Mentoring of High School Students - hosting high school students in research lab for one week periods 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Four high school students have had 1 - 2 week work placements and mentoring.
Year(s) Of Engagement Activity 2016,2017
 
Description NIDDK Workshop, Towards a Functional Understanding of the Diabetic Genome, Washington DC 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Thoughts on what are the main technologies and approaches that will deliver "a Functional Understanding of the Diabetic Genome" over the next 5 years.
Year(s) Of Engagement Activity 2018
 
Description Neonatal Diabetes Day - Exeter University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Presented a talk and took part in a debate.
Year(s) Of Engagement Activity 2014
URL http://www.exeter.ac.uk/research/feature/diabetes/
 
Description Neonatal Diabetes Day, Exeter University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Talk and debate about scientific reseach, with parents of patients with neonatal diabetes,
Year(s) Of Engagement Activity 2014
 
Description Participated in a CREST activity. 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Mentoring students.
Year(s) Of Engagement Activity 2016,2017
URL http://www.crestawards.org/
 
Description Public Engagement Lecture - The Academy of Medical Sciences, supper club, Norwich, UK. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation to the The Academy of Medical Sciences Supper Club, followed by debate.
Year(s) Of Engagement Activity 2016
URL https://acmedsci.ac.uk/grants-and-schemes/events/regional-events
 
Description Rachmiel Levine-Riggs Symposium, Los Angeles 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk at international diabetes research conference
Year(s) Of Engagement Activity 2020
URL https://www.cityofhope.org/research/levine-symposium/levine-symposium-program
 
Description YouTube video explaining results of research and publication in EMBO J 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact A video explaining in simple terms and didactic artwork the results of work in Kalisz et al, EMBO J, 2020
Year(s) Of Engagement Activity 2020
URL https://www.youtube.com/watch?v=FFBi4LZAXDM
 
Description ZENCODE-ITN Workshop Cape Sounio, Greece 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Developmental and medical genomics with animal models. .
The scientific focus of the ZENCODE-ITN consortium is to understand genome regulation through combined experimental and computational approaches in a model vertebrate. The consortium recognises the urgent need for highly skilled young scientists trained in both computational biology and experimental wet lab biology. This network provides multidisciplinary skills for a solid foundation in computational biology and developmental genomics.
The aim is to comprehensively annotate functional epigenetic and transcribed elements, decipher genomic codes of transcription, as well as coding and non-coding gene function during vertebrate development and enhance zebrafish as an attractive developmental, comparative genomic and disease model. The participants include major zebrafish genomics laboratories, eminent computational biologists and world-class genomics technology experts.
Year(s) Of Engagement Activity 2018