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
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.
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".
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".
People |
ORCID iD |
Keith Edwards (Principal Investigator) | |
Gary Barker (Co-Investigator) |
Publications
Winfield M
(2017)
High-density genotyping of the A.E. Watkins Collection of hexaploid landraces identifies a large molecular diversity compared to elite bread wheat
in Plant Biotechnology Journal
Tock AJ
(2021)
Crossover-active regions of the wheat genome are distinguished by DMC1, the chromosome axis, H3K27me3, and signatures of adaptation.
in Genome research
Raffan S
(2021)
Wheat with greatly reduced accumulation of free asparagine in the grain, produced by CRISPR/Cas9 editing of asparagine synthetase gene TaASN2
in Plant Biotechnology Journal
Przewieslik-Allen AM
(2018)
Developing a High-Throughput SNP-Based Marker System to Facilitate the Introgression of Traits From Aegilops Species Into Bread Wheat (Triticum aestivum).
in Frontiers in plant science
Przewieslik-Allen AM
(2021)
The role of gene flow and chromosomal instability in shaping the bread wheat genome.
in Nature plants
Osman K
(2021)
Distal Bias of Meiotic Crossovers in Hexaploid Bread Wheat Reflects Spatio-Temporal Asymmetry of the Meiotic Program.
in Frontiers in plant science
King J
(2017)
A step change in the transfer of interspecific variation into wheat from Amblyopyrum muticum.
in Plant biotechnology journal
Coulton A
(2020)
Segregation distortion: Utilizing simulated genotyping data to evaluate statistical methods.
in PloS one
Coulton A
(2020)
Examining the Effects of Temperature on Recombination in Wheat
in Frontiers in Plant Science
Burridge AJ
(2018)
Conversion of array-based single nucleotide polymorphic markers for use in targeted genotyping by sequencing in hexaploid wheat (Triticum aestivum).
in Plant biotechnology journal
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 | 06/2019 |
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 |