A multi-channel liquid handler for the Bristol Genomics facility

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

Abstract

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

The Bristol Genomics Facility collaborates closely with a number of groups at Bristol including the Cereals Functional Genomics group , who remain at the cutting edge of technology development; via collaborations with Affymetrix and LGC a number of commercially successful products have been developed and utilised 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 for multiple commercially important species following the installation of a 384-well Axiom GeneTitan high throughput genotyping platform in 2014 (ALERT 13). In 2015 the University provided funds for the facility to purchase both an Illumina MiSeq and NextSeq500 next generation sequencer. These various developments have resulted in the Facility processing over 120,000 DNA samples over the past four years. To continue to be at the forefront of technology development and application the Facility must maintain and improve its post-PCR sampling handling provision and procedures so that it is able to cope with the ever increasing demand for its services. Provision of a high throughput liquid handling instrument 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.

Technical Summary

Funds are requested to purchase a post-PCR multi-channel liquid handler together with a 3-year warranty.

The application to purchase the liquid handler 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 replacing and upgrading the existing facilities at Bristol include Dr Greg Jones' into food safety, Dr Kevin Kemp's research into the ageing brain, 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 Biomek i7 Multichannel Workstation is the most powerful and comprehensive Biomek available and it is the only high throughput liquid handling platform validated and approved by Thermofisher for the automated processing of Axiom High Throughput 96 & 384 format genotyping arrays (see email from Thermofisher). In addition, the Biomek i7 supports and complements a variety of other genomic applications run by the genomics facility including high throughput expression arrays and the support of automated next generation sequencing library construction methods. This is in addition to general post-PCR processing steps including nucleic acid quality control and quantitation, nucleic acid purification and size selection for example.

Planned Impact

The purchase of the post-PCR high throughput sample handling robot 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". In addition, in 2018 Prof. Edwards was jointly awarded (with Prof. Graham Moore, JIC) the Rank prise for nutrition, for his contribution to global wheat breeding via the provision of a wide range of SNP-markers and genotyping platforms.
 
Description High throughput genomics involving the processing and analysis of large numbers of samples has revolutionised the field of genetics, with molecular characterisation becoming increasingly important for a wide range of species and applications. Cutting edge genomics requires quick turnaround times from sample submission to data delivery so that results are quickly available for the next phase of research / experiments / trials. This need for 'immediate' data requires good quality, reliable, high throughput liquid handling equipment for 384-well format techniques in both pre- and post- PCR areas. We are therefore requesting investment into Bristol's post-PCR liquid handling to permit the continued use and significant extension of previous ALERT investments, to allow new protocol developments for the future, and to enable the Bristol Genomics Facility to continue to offer our user community access to a first-class research facility.
Exploitation Route The Bristol Genomics Facility has the equipment and necessary expertise for carrying out next generation sequencing (Illumina NextSeq500 and MiSeq plus Oxford Nanopore); Transcriptome microarray analysis (Thermofisher/Affymetrix GeneChip platform); Real-time quantitative PCR (Roche LightCycler 480 system); High throughput genotyping & expression arrays (Thermofisher/Affymetrix GeneTitan system; purchased via the ALERT13 scheme); Capillary sequencing and genotyping (Thermofisher/Life Technologies ABI 3500); Nucleic acid analysis and quality assessment (Nanodrop8000 spectrophotometer, Agilent TapeStation 2200 , BMG Labtech PHERAstar microplate reader and Thermofisher Qubit); for pre-PCR work a Biomek 4000 for the automatic preparation of sequencing libraries and a Covaris E220 Ultra-Sonicator both purchased via the ALERT 16 scheme. In addition, the facility has significant IT resources with over 30 Tb of backed up storage for customer data (to allow for 6-months of archival after data handover) and a dedicated web site. The facility is widely used by researchers from Bristol University and other UK and non-UK academic/commercial organisations.
Sectors Agriculture, Food and Drink,Healthcare,Manufacturing, including Industrial Biotechology

URL http://www.bristol.ac.uk/biology/genomics-facility/
 
Description The increased efficiency of the recently installed robotics within the Bristol Genomics Facility has led to increased throughput such that the facility has been able to offer its customers greater flexibility in how it handles their samples; customers who include UK wheat breeders, and international fish breeders.
First Year Of Impact 2019
Sector Agriculture, Food and Drink,Environment
Impact Types Economic,Policy & public services

 
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 BBSRC Flexible Talent Mobility Award (FTMA)
Amount £25,000 (GGP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 08/2019 
End 12/2019
 
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