1. Challenges facing biomedicine Data handling and mining Redefining disease Therapeutics

2. Challenges facing biomedicine Data handling and mining Bioinformatics Redefining disease Therapeutics

3. Challenges facing biomedicine Data handling and mining Redefining disease Based on biology Biomarker discovery and validation Therapeutics

4. Challenges facing biomedicine Data handling and mining Redefining disease Therapeutics Pathways Vs single molecules

5. Advantages of the UK NHS World class biomedical research base An educated populace A strong Pharma industry?

6. Advantages of UCLH/UCLP Huge and diverse population International class research focused hospitals A strong academic partnership model Proximity to World class research- UCL, Crick… Proximity to Pharma

7. Advances in biotechnology Finding all the genes

8. The requirements for translation Finding genetic variants

9. The requirements for translation Finding genetic variants  Proving causality  Clinical diagnostics 

10. The requirements for translation Finding genetic variants  Proving causality  Determining biological function

11. The requirements for translation Finding genetic variants  Proving causality  Determining biological function  Influencing that function

12. Genes to patients Genes Models & Mechanisms Patients

13. Patients to Mechanism Patients Determining biological mechanisms Prioritising genetic variation

14. Recruit people on “recall by genotype/phenotype” basis –Blood, possibly saliva/urine –Baseline questionnaire –Aim for ~60,000 in total 5 Themes –Neuroscience, cardiometabolic, infection and immunity, rare diseases (inc. cancer), general population BioResource principles

15. NIHR BioResource Joint project between Biomedical Research Centres/Units (BRC/Us) from Cambridge (lead site)Oxford UCLH/UCLImperial GSTT/KCLIoP/SLaM (KCL) Leicester Total funding of ~£30M over 5 years £1+M to UCL matched with BRC funds 7 posts

16. Running since 2005, has ~10k volunteers, mostly blood donors recruited through NHSBT Consented for use of DNA, including whole genome sequencing Recruits are recalled for Stage 2 studies based on genotype (+/- variant of interest)  Study pays for genotyping of collection prior to cohort selection  Experimental medicine studies, including industry Cambridge BioResource

17. 2-Staged Activity: o Stage 1 activity -Recruitment of new volunteers and patients to the bioresource o Stage 2 activity -Recall of existing members to stage 2 research studies

18. 7 posts for UCL BioResource: coordinator, 2 IT posts, 3 research nurses, 1 biobank technician Steering committee in place UCL is leading on Neuro Theme UCL will focus on disease cohorts UCL BioResource

19. Sample/Data Collection  Enrolment through our hospitals  Providing Informed consent  Sample collection is very light: 22.2ml blood sample (3 X 4.9ml EDTA tube & 1X 7.5ml Serum) for DNA / Serum/ Plasma isolation  Material used for identification and selection of suitable volunteers for stage 2 studies only-not for individual research purposes  Contact details collected-needed for recall purposes (email, phone numbers etc…)  Questionnaire data-health and lifestyle information used to aid selection process (e.g. BMI, medical history, smoking status etc…)

20. Aims  Everyone who comes to one of our hospitals is invited to participate  Improve patient and general population involvement in research  Use the human as the animal model  Champion UKs leadership in biomedicine  Engage with industry to speed translation  Driver of economic growth

21. Success will depend on Stage 2 studies  Face to face with PI/researcher to review and discuss finer details of study (contact details, suitability for blood collection, method of exchanging study updates etc..)  Draw up study summary sheets for nursing/recruitment team  Mail out to volunteers  Manage responses and incoming queries from volunteers  Liaise with researcher re: response rates and participation status  Volunteer follow up/chase up to meet recruitment targets  Volunteer feedback

22. Cambridge experience Stage 2 Research Activity: o 65 studies have approached CBR for support o 46 approved, 26 completed, 20 studies currently supporting o Actively recruiting to 14

23. Example 1:  GSK Study  CBR SAB approved  Recall based on single SNP (15% MAF)  Looking to recruit across all 3 genotypes  Comparator Drug study  Of the 12,000+ volunteers in CBR, 720 are eligible according to genotype

24. Additional Inclusion criteria include:  BMI greater than 25kg/m2  A score of 6 or higher on the Alcohol- Use- Disorders- Identification- Test (AUDIT)  Use of contraception methods until 14 days after last dose of medication Exclusion criteria include:  No known disease/diagnosis  Use of prescription and non-prescription drugs (vitamins, herbal remedies)  Vegetarians, vegans, religious dietary requirements  Heavy smokers Of the 720 volunteers suitable by genotype, 195 eligible for invite  Volunteer Commitment is 3 weeks in total  Screening visit (2-4hrs in duration)  Involving use of two drugs and placebo  X3 treatment periods 5 days each (x2 overnight stays, x3 full day admissions) The expected uptake rate of 10-15%  The target number is 48  Expect to achieve 29/48 recruits to study

25. Stage 2 Research Studies  Research studies supported across the disease themes (Cancer, neuro cardio….)  Range of commitments required from the volunteer  Less Intensive  Blood studies (Requiring single or multiple samples)  Online questionnaires  More Intensive  30hr fast (e.g. T2D)  Muscle biopsy/skin biopsy  One or more overnight stays  Dietary regime  Drugs/Biologicals

26. Classify stage 2 studies into 3 models: Model 1: Blood studies (involves single/multiple blood samples) Bioresource recruits, manages blood sampling, sends anonymised blood samples to researcher. Model 2: Phenotyping studies (involves researcher having face to face with volunteer) Bioresource recruits, contact information passed to researcher. Model 3: Drug studies (involves pharmacy arm and genotypes being known upfront) Bioresource recruits, contact information passed to researcher. Involves three way communication between Bioresource, the research recruitment team and pharmacy, genotypes passed to pharmacy not research recruitment team

27. Finding causal variants Genetics Influencing biology Humans Determining biology Models At risk Cohorts Few interactors Complex pathways Biomarkers Experimental Medicine The human as the animal model