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Science with Impact Science with impact Highlights 2019/20 What we do Our work Our approach Other information What we do Our work Our approach Other information World-class research and innovation that impacts people’s lives Read more about what we do at sanger.ac.uk 1 What we do Our work Our approach Other information What we do helps us to understand and improve all life. Gorilla hand Read how reconstructing a 50,000-year-old parasite gene reveals how malaria jumped from gorillas to humans on page 32 2 What we do Our work Our approach Other information Director’s Introduction As the UK Chief Medical Officer outlined in the 2019 report Health, our global asset – partnering for progress we live in a global village where the health issues of one country swiftly impact another. In this world, genomics – powered by open- access data sharing – is central to delivering the rapid, insightful information needed to shape successful therapies and effective healthcare delivery. As evidenced by the outbreak of the Covid-19 coronavirus, seamless and open sharing of genomic data is guiding international public health responses and powering the worldwide race to develop vaccines. Here at the Sanger Institute, we analyse malaria parasite genomes from both neighbouring countries and continents to track the emergence and spread of drug resistance, guiding public health strategies. By successfully pooling datasets on cancer samples, databases and analysis we can work with fellow scientists across continents to reveal the causes and potential treatments for tumours, driving the development of precision, personalised medicine. Research of this scale is a truly collaborative endeavour, both within the Institute, nationally and internationally. It is only through the tireless efforts of researchers in the field or in the wards to collect samples and phenotypic data, combined with the sequencing and computational skills of teams around the world, that we can make these scientific advances. To celebrate the invaluable work of our technicians to deliver science at scale, we are proud signatories to the Technician Commitment to develop the talents and careers of our staff. We are also delighted that our International Fellows scheme is enabling new continental networks of genomic research to grow and deliver science. To deliver truly seamless sharing of genomic and clinical data, we actively support the work of the Global Alliance for Genomics and Health (GA4GH) to create the protocols and frameworks needed to open up the world’s genomic databases to the global scientific community. Through innovations such as GA4GH Passports and Data Use Ontology, the process to gain access to much-needed data will now take a matter of days instead of weeks. As the impact of genomics is more broadly felt across society as a whole, the Institute plays a pivotal role in helping policymakers and clinicians understand and apply its power. The Institute has a long history of providing expert guidance to the UK’s policy makers and this year has been no exception, with our researchers advising the House of Commons Science and Technology Committee on Commercial Genomics and contributing to the Chief Medical Officer’s annual report. And our researchers have helped to shape online genomics training courses that, in conjunction with Wellcome Genome Campus Advanced Courses and Scientific Conferences, are enabling healthcare professionals to embrace genomic medicine. Genomic research is still in the foothills of extracting and using the knowledge buried in the six billion letters of code in the human genome. The ever increasing numbers of human genomes sequenced for research or clinical diagnosis will reveal patterns and motifs that will shape health and disease research for decades to come. When we also consider the rest of the genomes on Earth the potential is vast and the Sanger Institute will be in the vanguard of this revolution in science and society. Professor Sir Mike Stratton, Director Wellcome Sanger Institute 3 What we do Our work Our approach Other information At a Glance In 2019, we read the genomes of 313 species In 2019, the In 2019, we Sequencing Centre read the equivalent provided the equivalent of of one gold-standard (30x) human genome every 2,880 gold-standard 3.5 mins human genomes a week In 2019, the The human genome Sequencing Centre is approximately outputted an average of 31,000bn 3bn DNA bases base pairs a day Sequencing long Centre Data Centre Total number of Network backbone compute cores speed 45,000 400GB/sec approx Centre-based Usable storage high performance in the Data Centre compute cores 65-70Pb 25,000 approx approx Centre-based cloud-based flexible compute cores 20,000 approx 4 What we do Our work Our approach Other information 2019 timeline Cancer mutation resource reveals bursts of activity Genome read Global Strep A from just half a vaccine one mosquito-worth step closer of DNA 100 organoid cancer models developed 100 new gut Matt Hurles Nicole Soranzo bacteria elected Fellow honoured by discovered of Royal Society EMBO Molecular blueprint Genetic code of Gene mutations of early embryo WW1 soldier’s offer MRSA drug development cholera mapped options Jan Feb Mar Apr May Jun Ian Dunham Sanger Institute Peter Campbell becomes Open signs up to elected to Targets Director Technician Academy of Commitment Medical Combining Sciences ultrasound Sarah Teichmann with genomics wins 2020 CRISPR catches improves prenatal Biochemical critical cancer diagnoses Society award changes Sanger Institute joins Building blocks EDIS (Equality, of lungs mapped Diversity and Inclusion for first time in Science and Health) Crusaders made love and war 5 What we do Our work Our approach Other information Baby biome shows vaginal Drug targets delivery boosts for liver-stage maternal bacteria malaria found transfer Three CT scans Mathew Garnett could promote receives National cancer Cancer Research development Institute Excellence Award Jumping genes can cause rare 140 genes linked Genomes reveal developmental to immune system Africa’s malaria disorders control control is at risk Pathway to colon Successful merge Malaria Cell Atlas cancer mapped of cancer datasets reveals parasite’s creates secrets at every Measles wipes the comprehensive stage of life cycle immune system resource Jul Aug Sep Oct Nov Dec Institute research Sanger scientists Wellcome funding featured in CMO’s support LifeLab drives project report event across to map all life in East Anglia Britain and Ireland Genomic monitoring Sanger Sam Behjati is shows spread of co-sequencing recognised with multidrug-resistant 450,000 genomes early career malaria in Asia for UK Biobank research award Houses of Brown Trout Parliament Select genome may Committee reveal species’ evidence on superpowers Commercial Genomics 50,000-year-old Missing gene gorilla to human reveals two IBD malaria gene pathways resurrected Diarrhoea-causing bacteria adapted to spread in hospitals 6 What we do Our work Our approach Other information Year in Numbers 568 17.78 research Petabases articles in 2019 Cell 8 7.398 Pb Lancet 1 4.639 Pb Nature 20 3.025 Pb 1.910 Pb Nature Genetics 21 Jan 2016 Jan 2017 Jan 2018 Jan 2019 Jan 2020 Science 10 Who published Where Sanger How much DNA our work? staff are from* was sequenced? 1,199 Europe 51 North America 8 Middle 94 East 14 Asia Pacific 16 Africa Latin America *In January 2020 7 What we do Our work Our approach Other information Our work is at the forefront of genomic research. With secured funding from Wellcome, we are able to strategically focus our work in five key research fields 8 What we do Our work Our approach Other information Tree of Life Discover how we enable researchers to study life at the most intimate detail on page 36 9 What we do Our work Our approach Other information Cancer, Ageing and Somatic Mutation The team studied cells from 2,035 colon ‘crypts’ Samples read with 1,000x less DNA than previously In this section 1 and then fully automated the process 1 Uncovering the pathway Uncovering enabling tens of thousands of genomes to colon cancer to be swiftly sequenced. The method has the pathway to since been adapted for other projects where 2 Why it’s never too late only tiny amounts of DNA are available, for to stop smoking colon cancer example in studies of parasites. 3 Medical imaging radiation The hidden world of genetic mutations In the colon study, published in Nature, promotes cancer capable cells in healthy colon tissue has been researchers found mutations that uncovered. Sanger researchers shed represent the very earliest stages of cancer 4 Dismantling cancer to find light on the very earliest stages of development. The cells were morphologically its weak spots cancer and help to understand how a normal, but had distinct patterns of genetic healthy cell becomes a cancerous one. changes, including in genes known to drive 5 Cancer drug data will power cancer growth. next wave of discovery Researchers at the Sanger Institute have developed technology to sequence the The team also uncovered mutational 6 CRISPR catches out critical genomes of small numbers of cells, allowing signatures in the cells – tell-tale patterns, cancer changes them to study genetic mutations in or ‘fingerprints’ of specific DNA changes unprecedented detail. caused by a specific carcinogenic chemical 7 Clarifying mutations in the driving seat or process. Some signatures were ubiquitous The team studied cells from 2,035 colon and continuous, others were present in only 8 Cancer causing culprits will be ‘crypts’, the tiny cavities that form colon a few individuals, in particular crypts or during caught by their DNA fingerprints tissue. They developed a method to certain periods of life. Six signatures had sequence DNA from just a few hundred cells never been seen before, and further 9 International scientists come together at a time, using over 1,000 times less DNA research is needed to determine their for unprecedented exploration of than standard protocols.
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