The MRC DNA Bank: the story so far - PowerPoint PPT Presentation

1 / 37
About This Presentation
Title:

The MRC DNA Bank: the story so far

Description:

Uppsala 13 September 2002. Mission statement. The MRC's ... collectors to share even an aliquot of their sample plus associated phenotypic/clinical data? ... – PowerPoint PPT presentation

Number of Views:227
Avg rating:3.0/5.0
Slides: 38
Provided by: geo136
Category:
Tags: dna | mrc | aliquot | bank | far | story

less

Transcript and Presenter's Notes

Title: The MRC DNA Bank: the story so far


1
The MRC DNA Bankthe story so far
  • ESF Workshop on Biobanks
  • practical, ethical and legal aspects

Uppsala 13 September 2002
2
  • Mission statement
  • The MRC's mission is set out in its Royal
    Charter
  • To encourage and support high-quality research
    with the aim of maintaining and improving human
    health
  • To train skilled people, and to advance and
    disseminate knowledge and technology with the aim
    of meeting national needs in terms of health,
    quality of life and economic competitiveness
  • To promote public engagement with medical
    research

3
Medical Research Council
50 Institutes and Units UK
Human Genome
Mapping Project
Resource Centre an MRC Unit
with three divisions
4
Unit Divisions
UK HGMP RC www.hgmp.mrc.ac.uk
Research
Bioinformatics
MRC geneservice
  • Software
  • development
  • Research products
  • and services
  • Functional
  • genomics

5
MRC geneservice mission
  • To develop and provide at cost-recovery
    innovative functional genomic products and
    contract research services
  • for the European academic and commercial research
    community
  • to improve human health

6
Key Points
  • Objectives
  • Non-restricted access
  • Unique genomic resources
  • Enabling technologies
  • Cost recovery
  • Value for money
  • Invest in infrastructure
  • Offering
  • Products and services
  • Functional genomics
  • Translational research
  • Market
  • Academic and commercial
  • Public/private partnering

7
Business Model
  • Short term
  • Products and contract research
  • RD via collaborations/grants
  • Strengthen products and service offering
  • Increase volumes/market share
  • Full cost recovery by 2006
  • Long term
  • Growth in internal research
  • Partnering/Joint Ventures
  • Develop IP portfolio

8
Organisation
  • Moved to Babraham July 2001
  • Non-profit government organization
  • Bioinformatics and RD support at Hinxton
  • Commercial infrastructure
  • 32 staff
  • Operations/IT/Finance/Business Development

Cam Ba Hi
9
Recent highlights
  • Commercial Development
  • Business Plan Feb 01
  • Premises at Babraham July 01
  • Commercial team in place Dec 01
  • MRC Board accepts budget and business strategy
    Apr 02
  • MRC geneservice launched May 02

10
Recent Highlights
  • Product and Service development
  • RNA Service
  • 1st academic and commercial Affymetrix Microarray
    service provider in UK Dec 01
  • 1st commercial deal May 02
  • Quantitative PCR validation of microarray
    results July 02
  • Cloning Service
  • Pilot production line of expression ready clone
    (mouse cancer ORF set) Aug 02
  • DNA Service
  • 1st commercial SNP genotypng deal April 02
  • National DNA banking award July 02
  • Reagents
  • C. elegans RNAi clones, ScFv library, RIKEN FL
    mouse clones, MGC FL Human cDNAs

11
Global distribution
gt 11,000 users in gt 40 countries Web ordering
system Online product description 3 day
turn-around
12
DNA Service
  • DNA extraction
  • Fresh frozen whole/separated blood
  • Mutation Detection and SNP Validation
  • PSQ WAVE HPLC sequencing
  • Genetic studies
  • Linkage and association studies
  • HTP microsatellite SNP typing pipeline
  • Provide access to
  • Technology and analysis tools
  • Training
  • Genetics network
  • 18 collaborations
  • Immunology, cardio-vascular, neurological, cancer
    studies

13
Genotyping platform - TaqMan
Liquid handling Water bath PCR
Acquire data analyse
Current daily throughput 1 FTE 100 x 384-well
plates 38K assays 95 call rate (variable DNA
quality) 100 concordance
14
Laboratory Information Management System
4R
replicating re-arraying recording reporting
  • Allows users to create a system to track a
    laboratory process
  • Allows users to define annotations for samples
  • Provides a repository for results
  • Provides reports
  • Provides an audit trail
  • Maintains need-to-know security

15
DNA Service work in progress
  • Planning and starting to build a DNA bank

16
Milestones on road to DNA Bank
  • October 2000 MRC funds 13 collections
  • December 2000 MRC calls for proposals for a UK
    network for DNA sample banking and genotyping
  • May 2001 MRC workshop on its initiative
  • July 2001 MRCg et al submit proposal
  • July 2002 MRC selects MRC geneservice as a DNA
    banker

17
13 collections funded by MRC in October 2000
  • Age-related macular degeneration families
  • Colorectal cancer cases, relatives, matched
    controls
  • Hypertension nk
  • Parkinsons disease nk
  • Multiple sclerosis cohort
  • Asthma and eczema family collection
  • Acute coronary event families
  • Type 2 diabetes nuclear familial
  • Acute leukaemia MRC clinical trials patients
  • Unipolar depression case control study
  • Glomerulonephritis cases
  • Breast cancer affected sib pairs
  • Late onset Alzheimers disease case control study
  • 40K samples being collected
  • Each applicant already has appropriate ethical
    approval
  • Grant conditions require collections to be placed
    in MRC DNA banking centres
  • Most collectors have well-supported labs and
    international reputations

18
MRC call for UK network Dec 2000
  • The MRC
  • recognises importance of genetic epidemiology in
    the post-genome era
  • announces its aim of establishing a network of
    centres
  • envisages network as part of the Biobank
    infrastructure
  • the network will
  • have custody of large DNA collections
  • manage the collections
  • integrate data systems across the network
  • common standards and practice
  • pilot high throughput genotyping
  • Network resources to be made available to UK
    scientists

19
MRC call for UK network
  • Scope of network
  • initial storage capacity 100,000 samples
  • potential to expand to manage other studies
    funded by MRC - or others with cost recovery
  • geographically clustered groups encouraged to
    form consortia
  • long-term national HT genotyping service
  • Assessment of bids
  • Two stage review to differ from normal peer
    review process
  • 1. consortia to express interest experts were
    to select a short-list
  • 2. selected consortia to submit work plans that
  • ? ensure users needs are met - including
    ready access to samples
  • ? demonstrate commitment of hosts

20
Expression of interest from Cambridge
  • Summary of expertise available in Cambridge
  • and of experience with large projects
  • Submitted from
  • 3 MRC units in Cambridge
  • 11 University of Cambridge departments (including
    two MRC 13 collector PIs)

21
Cambridge application for MRC DNA Bank July 2001
Institute of Public Health
other Cambridge groups including Sanger
Institute
22
Overall bank organisation
DoH/MRC/ MRC
COREC WT
DNA
BANKERS
Materials Operations
and Methods Committee
Group
OPERATIONS
23
Operations organisation
IPH UK
HGMP RC ECACC
Operations

Systems and Cell and
Genotyping Services Data
Group DNA Group Group
Research

Group
24
Work flow
DNA
Bankers blood samples Blood
DNA Storage Retrieval Tests
Analysis

Archive WGA QC/QA
Lines
Operations
automated steps (to be introduced one at a time)
25
MRC selects centres March 2002
26
MRC DNABankingNetwork
27
Combined application June 2002
The MRC DNA Bank service will comprise  organis
ing with the collectors the despatch of samples
from their subjects  receipt of subjects blood
or DNA samples (or receipt of samples from
ECACC)   extraction of DNA   housing of
DNA ? standard DNA concentration and DNA
quality determination
28
Questionnaire to collectors
  • Questionnaire probed status of collections
  • - all at different stages some not started
  • - some collectors query the custody status of
    samples
  • - different protocols

29
Current status of DNA Bank
  • Final negotiations are underway
  • MRCg and CIMR will use existing DNA extraction
    facilities
  • Standardised sample storage systems will be used
  • ECACC and CIMR will seek to improve EBV
    immortalisation
  • MRCg will develop and implement WGA
  • MRCg and CIMR will improve aspects of SNP typing
  • MRCg hopes to acquire an advanced storage system
  • Also MRC is to support a distinct collectors
    consortium

30
Matters arising
  • Should a national DNA bank be set up before or
    after collections have been funded?
  • Should a strategic national project conceived
    centrally be selected from proposals conceived
    locally?
  • Is it realistic to expect geographical clusters
    to form in preference to expedient clusters?
  • Is there an overwhelming need for a network?
  • In what ways might the network be part of the
    Biobank infrastructure?
  • How can we overcome the reluctance of collectors
    to share even an aliquot of their sample plus
    associated phenotypic/clinical data?

31
Should a national DNA bank be set up before or
after collections have been funded?
  • Organisational factors
  • If custody of samples and data sharing is not
    readily resolved, then fund collectors first
  • Scientific factors
  • Our data provide evidence that HT genotyping
    requires consistent quality DNA. As DNA/rx
    falls with UHT genotyping, we believe this will
    become an absolute requirement for high call
    rates and concordance

32
Should a strategic national project conceived
centrally be selected from proposals conceived
locally?
  • This depends on the extent to which the project
    will directly innovate or discover the more the
    amount of innovation / discovery anticipated, the
    greater the need for local proposals. A danger
    exists that local proposals may second-guess
    central conceptions so that the best guess wins.
  • NB the distinction between vertical and
    horizontal projects is useful post hoc

33
Is it realistic to expect geographical clusters
to form in preference to expedient clusters?
  • Competitive bidding for funds will tend to favour
    the creation of clusters (i.e. consortia) that
    most readily create the strongest possible bid on
    scientific grounds. The Cambridge bid was mainly
    geographic but not in the sense MRC intended.
    The non-Cambridge applicant is located 200 km
    away.

34
Is there an overwhelming need for a network?
  • The trend in large pharma genotyping projects is
    toward out-sourcing and toward complete
    centralisation. This is for reasons of
    capital/labour costs and data quality
    respectively.

35
In what ways might the network be part of the
Biobank infrastructure?
  • The network will achieve harmonisation of
    procedures and ensure full interactivity of data
    systems. It is essentially a collaboration. This
    may meet some of the needs of Biobank.
  • We are confident the MRC geneservice DNA bank
    will have the experience, processes and equipment
    needed to satisfy Biobank and others.

36
How can we overcome the reluctance of collectors
to share even an aliquot of their sample plus
associated phenotypic/clinical data?
  • There has to be a quid pro quo.
  • Well-supported collectors are more independent in
    their operations than less well-supported
    collectors. For the latter, a bank network has
    more to offer. One may predict that in future
    collectors including the MRC 13 will all
    understand the virtues of a division of labour.

37
Acknowledgements
  • Nick Day Doug Easton - IPH Cambridge
  • David Lewis Bryan Bolton - ECACC
  • Bill Ollier Jane Worthington - CIMR Manchester
  • Duncan Campbell Tom Weaver - UK HGMP / MRCg
Write a Comment
User Comments (0)
About PowerShow.com