High throughput sample handling for high throughput genomics

Lead Research Organisation: University of Bristol
Department Name: Biological Sciences

Abstract

Funds are requested to purchase a High Throughput Sample Handling Suite together with a 5-year warranty.

The application to purchase the suite has been instigated by Professor Keith Edwards, the academic director of the Bristol Genomics Facility, following discussions with several researchers and industrial partners both at Bristol and beyond. Researchers who would directly benefit from installing the Suite at Bristol include Dr Amanda Churchill's Bristol-based research into ageing and wellbeing, Professor Ian King's Nottingham-based research into food security, Dr Alison Bentley's research into food security at NIAB and Dr Chris Burt's wheat breeding at RAGT to address issues associated with food security.

All of these cases are in addition to Professor Keith Edwards' own extensive research into wheat breeding and its relationship to food security and Dr Gary Barker's research in metagenomics

The scientific cases for support all require high throughput sequencing and genotyping; the high throughput sample handling suite enables this on a scale required for genome wide applications such as genotyping by sequencing and genome scanning.

The high throughput handling suite consists of two main components; 1. The Biomek 4000 is a liquid handling workstation supporting a variety of applications including DNA extraction, amplification, setup, sample dilution and normalization, 2. The Covaris E220 is a focussed ultra-sonicator capable of multi-sample, batch preparation, and processing a wide range of sample types and volumes. The E220 may be programed to process up to 96 samples in a single batch each with variable sonication requirements and volumes. This makes it possible to bring the advantages to numerous biological and chemical applications including, DNA which is a standard part of genomic DNA library preparation methods for next generation sequencing. Whilst there are other automation platforms available, we are requesting one that provides maximum flexibility to feed into existing pipelines and support the development of new applications, as opposed to closed system robotics which would limit the usage of the investment

Technical Summary

Genomics technologies, specifically sequencing and genotyping, continuous to witnessed exciting developments in both increased scale and reduced costs.

The Bristol Genomics Facility has, and remains, at the cutting edge of technology development; via aits collaborations with Affymetrix and LGC is has developed and utilised a number of commercially successful products such as the Axiom 820K wheat high density array and the Axiom 35K wheat breeders array. These developments have resulted in Bristol becoming a centre of high throughput genotyping. In 2013 the University provided funds for the facility to purchase both a MySeq and a NextSeq next generation sequencer. These various developments have resulted in the Facility processing over 34, 000 DNA samples over the past two years. To continue to be at the forefront of technology development and technology application the Facility must improve its sampling handling procedures so that it is able to cope with the ever increasing demand for its services. Provision of a high throughput sample handling suite would enable to Bristol Genomics Facility to both develop new strategies (such as targeted genotyping by sequencing) and expand the number of applications that it can offer its internal and external users.

Planned Impact

The purchase of the high throughput sample handling will have a significant impact on many of the users of the Bristol Genomics Facility, specifically on their ability to carry out cost effective high throughput sequencing and genotyping. As the Facility is open to all users both within and beyond the University (non-Bristol users have included the John Innes Centre, Rothamsted Research, Nottingham University and Aberystwyth University), installation of the suite will impact on the maximum number of researchers possible and enable research across a wide area of the scientific portfolio of the BBSRC, including wheat, humans and a range of other species of relevance to the BBSRC.

As the wheat breeding company RAGT has indicated that they will make use of the suite if it is installed at Bristol, the impact of the purchase will extend beyond the academic environment and hence could have a significant on the ability of UK wheat breeders to develop the next generation of elite wheat varieties having improved agronomic traits such as enhanced disease resistance and/or increased yield.

The Edwards group has an excellent track record of generating science with impact, for instance, it has recently delivered to the wheat breeders a large amount of genomic sequence, and a large number of SNP markers (>820,000 to date), all in a usable form and without any associated IP (via the public database held at CerealsDB). In addition it has, and continues, to work with the genotyping company's Affymetrix and LGC to develop further molecular markers, which are being used by both companies to provide commercially successful services to wheat breeders and academics alike (see the web site of both companies for further details). The current BBSRC funded WISP has continued to develop further SNP resources further and has on its steering committee, all the major wheat breeding companies. In recognition of Prof. Edwards' contribution to UK agriculture the Royal Agricultural Society of England awarded him their 2011 Research Medal, a Medal which acknowledges "research work of outstanding merit, carried out in the United Kingdom, which has proved or is likely to be, of benefit to agriculture".

Publications

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Coulton A (2020) Examining the Effects of Temperature on Recombination in Wheat. in Frontiers in plant science

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Burridge AJ (2017) High-Density SNP Genotyping Array for Hexaploid Wheat and Its Relatives. in Methods in molecular biology (Clifton, N.J.)

 
Description Equipment currently being installed
Exploitation Route To early to say
Sectors Agriculture, Food and Drink

 
Description Problems caused by introgessions
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
Impact Wheat breeding companies were made aware about the effect that introgressions have on recombination and why this may lead to difficulties in the future, this has caused some companies to re-examine their breeding strategies
 
Description A pipeline for efficient recombination in wheat
Amount £200,364 (GBP)
Funding ID BB/W003317/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 09/2021 
End 03/2023
 
Description International workshops
Amount £10,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2019 
End 08/2019
 
Title Introgression plotter added to Cerealsdb 
Description Software to allow users to screen wheat germplasm for potential introgressions from wheat relative 
Type Of Material Data analysis technique 
Year Produced 2019 
Provided To Others? Yes  
Impact At the request of the wheat breeding companies we have made this tool available via Cerealsdb so that breeders can check on the presence of possible introgressed regions in the bread wheat genome 
 
Title QTL database 
Description Upload of QTL database to Cerealsdb 
Type Of Material Data analysis technique 
Year Produced 2019 
Provided To Others? Yes  
Impact Breeders and academics are now able to download/examine various QTL-based datasets 
 
Title Upgrade to cerealsdb (cerealsdb3) 
Description We have carried out a significant upgrade of cerealsdb to include new analytical tools and a much larger data set 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
Impact Increased level of data downloads and use of tools to detect introgressions in wheat 
URL http://www.cerealsdb.uk.net/cerealgenomics/CerealsDB/indexNEW.php
 
Description Collaboartion with Syngenta to exchnage knowledge on trasformation and double haploid production 
Organisation Syngenta International AG
Department Syngenta Ltd (Bracknell)
Country United Kingdom 
Sector Private 
PI Contribution exchange of personal to improve our technology in double haploid production
Collaborator Contribution Spent time at Syngenta providing input into transformation technolgy
Impact Better transformation and double haploid technology available to Bristol
Start Year 2019