2011: Unlocking genomes' secrets

Highlights of the Institute's research and activities over the past year

In 2011, the Wellcome Trust Sanger Institute made new discoveries in areas of human disease and infection that ranged from new pathways in cancer and uncovering cholera's source, to finding the key used by malaria to unlock blood cells and carrying out surgery at the DNA level. In so doing, our researchers published more than 300 papers, read many billions of letters of genetic code and laid the foundations for worldwide genetic research.

Uncovering new cancer clues

In January, Institute researchers described how cancer can progress through a catastrophic process they called 'chromothripsis'. Until now, it has always been thought that cancer develops in a steady, stepwise fashion. But our cancer genome programme discovered that some cancers develop in a much faster fashion.

The team found that a single catastrophic event can shatter the strands of DNA in a cell into hundreds of fragments. This results in mutation of the cell's DNA on a massive scale. The scars of this chromosomal crisis are seen in people with all the common cancer types, accounting for at least one in forty of all cancers. This catastrophe is particularly common in bone cancers, where the distinctively ravaged genome is seen in up to one in four cases.

Conducting surgery at the DNA level

A SH-iPSC Colony on STO feeders.

A SH-iPSC Colony on STO feeders. [Genome Research Limited]


To discover genes involved in basic cellular processes as well as diseases such as cancer, the Institute's researchers work with mice and zebrafish to understand the effects of switching off individual genes in embryonic stem (ES) cells and developed tissues. Our understanding of gene function has been accelerated by our development of highly efficient techniques to knock individual genes in mouse and zebrafish. The resources we produce support much of the research at the Institute and are used widely around the world.

Taking mature cells such as skin cells and taking them back to their embryonic form is an important and growing area of research. These cells can be manipulated to correct a mutation before being grown into new mature tissues such as muscle, brain or nervous tissue. Stem cell technologies will underpin more of our research and the Institute's teams have developed new methods to improve the efficiency of cell reprogramming. This year has seen a great enhancement in the advancement of stem cell technologies. Our researchers have increased the efficiency of cell reprogramming to form stem cells by one hundred-fold and generated cells of a higher quality at a faster rate.

The potential of this research was demonstrated in October when Institute researchers announced that, for the first time, gene therapy had been used to cleanly correct a gene mutation in mice stem cells. They were able to correct a mutation responsible for liver disease and lung emphysema and show that the corrected gene worked normally in a mouse model.

Discovering the origins of disease

Children swimming in the sewage infected Bay of Bengal, the source of the latest cholera pandemic.

Children swimming in the sewage infected Bay of Bengal, the source of the latest cholera pandemic. [Dr Nick Thomson]


Next-generation sequencing made a dramatic impact on disease-causing organisms over the past year. Our researchers used this technology to read the DNA of cholera bacteria taken from people around the world and use this to track the spread of the latest cholera pandemic back to its source. They showed that the cholera type responsible can be traced back to an ancestor that first appeared 40 years ago in the Bay of Bengal. From this ancestor, cholera has spread repeatedly to different parts of the world in multiple waves.

This technique was also used to trace and explain the spread of H1N1 influenza pandemic by our researchers. Researchers discovered that the 2009 swine flu pandemic virus was already circulating in the UK before the first case was clinically identified and that the first pandemic wave was not caused by a single infected carrier bringing the disease in but by multiple introductions of the virus. Such insights may help with health prevention planning for future pandemics.

Our view of how the malaria parasite gains entry into the red blood cell - a vital step in the disease - was changed completely by a key discovery at the Institute. Our researchers discovered that the malaria parasite relies on a single receptor to invade the red blood cell. They also demonstrated that disrupting this interaction completely blocked the parasite from gaining entry into the red blood cell.  By identifying this interaction between the parasite protein and the host receptor we hope that it will be possible to develop an effective vaccine around the parasite protein.

Exploring the consequences of difference

A key technique used by Institute researchers to understand human disease is to scan rapidly the entire DNA of individuals to look for differences that could be associated with a particular disease. However not all of these variants are a true association and our researchers have found a way to select those most likely to be relevant. By studying the structure of the genome itself they identified regions that had the potential to be active in a particular tissue.

Our researchers were also involved in the identification of new genetic variants involved in the formation of platelets and more importantly, defined the function of genes near these variants using a series of biological analyses in fruit flies and zebrafish. These genes could be used in the future as new targets to develop better and safer platelet inhibitors for treatments of patients with heart attacks or strokes. This study provided a paradigm for how to successfully translate genome-wide association studies into function.

Sequencing Landmarks

All the genetic research at the Institute is made possible by the enormous leaps forward made in sequencing technologies. It took thirteen years to first read all of the DNA code of one human, now we can read the equivalent of one every hour. To put this into context the human genome is three billion letters of DNA long and in July 2011, the Institute celebrated having read more than 100,000 giga bases from many different species.

Partnering with the NHS

Deciphering Developmental Disorders logo

Deciphering Developmental Disorders logo [DDD]

In March 2011, the 'Deciphering Developmental Programme' (DDD) was launched to improve the diagnosis and understanding of developmental disorders at the genetic level. Over the next five years, the scientists and clinicians behind DDD hope to recruit to the study up to 12,000 children who have a serious delay in their physical or mental development or are born with multiple malformations. By capturing information on genetic make-up and physical and mental characteristics, the research team aims to improve diagnosis of conditions that affect around one in one hundred births in the UK. The project is a direct collaboration with all 23 of the NHS Clinical Genetics Services from across the UK together with the Wellcome Trust Sanger Institute.

Notable awards

The work of Institute researchers has been honoured with highly coveted awards. Dr Richard Durbin was awarded a fellowship by the International Society for Computational Biology. The ISCB Fellows program was created in 2009 to honour society members who have distinguished themselves through outstanding contributions to the fields of computational biology and bioinformatics.

Dr David Adams was awarded a Cancer Research UK Fellowship for his research into colorectal cancer. The six-year-long grant is given to new investigators who are set to become the eminent cancer scientists of the future.

Professor Gordon Dougan became the third member of faculty to be elected to the European Molecular Biology Organization. This tribute is recognition for the great contribution Gordon has made throughout his career to molecular biology.

Dr Eleftheria Zeggini was recognized in a pan-Europe award scheme for researchers at the early stages of their career. The European Research Council awarded Eleftheria with a grant to support her research into the genetics of common disease in humans.

Reaching out to society

The Institute launched other projects both internally and externally in 2011 aimed to encourage informed discussion about issues relevant to Sanger Institute research. Our Public Engagement Team launched the Malaria Challenge, a research tool used by students to provide information on the disease as well as different malaria control methods. They also collaborated on a project, Genome Futures, that allowed local students to quiz a panel of Sanger Institute researchers in a live web chat over two days. This event marked the 75th anniversary of the Wellcome Trust.

Other projects launched internally are the Sex in Science series and the Society and the Personal Genome debate series. Sex in Science is a programme that includes a series of talks by successful scientists who can share with us their career experiences and aims to raise awareness amongst men and women of issues facing women (and increasingly men) in science. Society and the Personal Genome programme's goal is to produce a coordinated programme of entertaining, controversial and thought provoking activities to encourage people to discuss the possible issues, benefits and drawbacks that are associated with genetic advance. Both of these programmes will continue into 2012.

Into 2012

Looking to the year ahead, the Institute will focus on investigating a broad spectrum of diseases and opportunities to develop its discoveries into treatments and diagnostic tests while maintaining its focus on discovery and basic science. In addition, as genetic knowledge and discoveries become part of mainstream cultural discourse, the Institute will seek to engage with a wide range of publics, to help develop interest and understanding of the potential and challenges of the fast-moving world of genetic research.

* quick link - http://q.sanger.ac.uk/2011revi