New research will tackle causes of disease from the UK to the tropics

Scientists at the Sanger Centre near Cambridge are aiming to understand the genetic make-up of micro-organisms responsible for some of the world's most common and sometimes, life-threatening, diseases.

£4,254,527 has been announced by the Wellcome Trust, through its Beowulf Genomics initiative, to sequence the genomes of Burkholderia pseudomallei, Neisseria meningitidis serogroup C, a significant proportion of Leishmania major and a project, jointly funded with Edinburgh University, to compare the sequence of Caenorhabditis elegans with those of important parasitic nematodes by expressed sequence TAG-based discovery.

Burkholderia pseudomallei is the cause of a disease known as melioidosis. It largely affects populations in South East Asia and Australia with Thailand reporting the greatest number of cases annually. Symptoms vary from localised abscesses to pneumonia and septicaemia. Sequencing of the two chromosomes that make up the organism is expected to take two years and will underpin future work to devise vaccines and treatments.

The Leishmania pathogen has many different strains which threaten the lives of some 350 million people mainly in the tropics and subtropics. It commonly causes disfiguring skin lesions leading to the destruction of the mucous membranes in the nose, mouth and throat cavities. A fatal form involves severe weight loss and anaemia with severe swelling of the spleen and liver. Sanger Centre scientists have sequenced chromosome 4 under a Beowulf-financed pilot and been working as part of a European consortium to sequence around 11.5% of the Leishmania major genome. The new funding will enable 15 of the organism’s 36 chromosomes (around 53.6%) of the genome to be fully sequenced. Together with other international projects, this will enable the entire genome to be completed within three years.

Having successfully sequenced the genome of a Neisseria meningitidis serogroup A strain, the Sanger Centre has now been granted funding for a serogroup C strain. This strain is the most common cause of meningococcal meningitis in adolescents and is the strain against which the current vaccination programme is being targeted.

“When the work is completed, we will have available finished sequences of the genomes for the most virulent strains of serogroups A, B and C. The next step will be to get the genome sequence of a strain that never causes disease and compare them so that we can understand why certain strains are able to cause such devastating disease.”

Professor Brian Spratt from the Wellcome Centre for the Epidemiology of Infectious Diseases at the University of Oxford

The parasitic nematode project will compare the genetic sequence of C. elegans with those of five parasitic worms responsible for infection in both humans and animals – notably sheep. Researchers aim to identify 10 000 genes from each of the parasites which should lead to hundreds of new drug targets and potential vaccines.

“In line with its established policy, The Sanger Centre will release sequencing data from these projects onto the internet as soon as it is available. This will ensure that other scientists and researchers throughout the world have immediate and free access to vital information that can help them to develop more effective treatments.”

Bart Barrell, Head of Pathogen Sequencing at the Sanger Centre

More information

1. Beowulf Genomics is a non-profit collaborative initiative set up by the Wellcome Trust to sequence the genomes of bacteria which cause some of the world’s most significant infectious diseases.
   Web site: www.beowulf.org.uk.
2. The Wellcome Trust is the world’s largest medical research charity with an annual spend of some £600 million in the current financial year 1999/2000. The Wellcome Trust supports more than 3,000 researchers at 300 locations, in 30 different countries – laying the foundations for the healthcare advances of the next century and helping to maintain the UK’s reputation as one of the world’s leading scientific nations. As well as funding major initiatives in the public understanding of science, the Wellcome Trust is the country’s leading supporter of research into the history of medicine.
3. Burkholderia pseudomallei: Dr. Bart Barrell, Sanger Centre in association with Dr. Rick Titball, DERA and Dr. Ty Pitt, Central Public Health Laboratories.
4. Leishmania friedlin: Drs. Bart Barrell and Alisdair Ivens, Sanger Centre in association with Professor. Jenefer Blackwell, Cambridge University and Professor Deborah Smith, Imperial College, London
5. Neisseria meningitidis C: Dr. Bart Burrell, Sanger Centre in association with Dr. Mark Achtman, Max Plank Institut for Molecular Genetics, Berlin
6. Parasitic nematodes EST project: Dr. Mark Blaxter, University of Edinburgh in association with Dr. Bart Barrell, Sanger Centre.