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Genetics - The fight against pollution, disease and crime

Leicester Geneticists Work Towards a Better Quality of Life

 

As the only university genetics department to have achieved the top rating of 5* in the latest Government Research Assessment Exercise, and with current research income in excess of £12 million, the University of Leicester Department of Genetics is a world leader in its field.  Head of Department Dr Annette Cashmore writes below about the Department’s strengths and why Genetics research is something that affects us all.

“At the University of Leicester we are at the forefront of research in many areas of genetics, especially those that affect society and human welfare.

 

It was here in September 1984 that Professor – now Sir – Alec Jeffreys discovered DNA fingerprinting, which has had a worldwide impact on both science and society, including the areas of crime detection, paternity cases and historical identification.

 

While there may yet be further applications in forensic analysis, work has now moved on to the development of new methods to study heritable changes in DNA, such as looking at the evolution of human DNA in real time, an exciting, revolutionary prospect. We are also investigating the impact of environmental agents on mutation in situations such as those following the Chernobyl disaster of 1986, while on a global front our research is informing international radio-biological protection policy. Other research areas where we are national or international leaders include:

 

·       Behavioural genetics - how our biological clocks work, for instance when we are affected by jet lag or shift work. 

·       Studies on the Y chromosome  -  throwing valuable insights on evolution theories and population histories.  

·       Medical Genetics -  the role of DNA in inherited disorders, such as deafness, birth defects and blood disorders, leading to new diagnostic tests and enhanced patient welfare.

·       Genome sequencing and analysis -   Yeast was the first eukaryotic cell (ie a cell that can be compared to human cells) to have its genome sequenced and members of the Department played leading roles in this international project. This has led to new insights into genome organisation in general and provided excellent models for aspects of  human genetics. Another genome sequencing project in which members of the Department of played a driving role is that of campylobactor, a bacterium that causes food disease - unpleasant enough in the West but a major source of concern in the developing world.

 

Something we value is the synergy between research and teaching. Our fifteen senior members of staff are all researchers of national and international standing and we all teach. So our undergraduate and postgraduate students and young scientists enjoy the experience of rubbing shoulders with world leaders as they are taught, and work with them in the lab.

 

We also work hard as a department to raise public awareness of science, through such outlets as the BA Festival of Science – recently held at the University of Leicester. As well as holding adult education courses, our staff go into schools and run taster courses at the University for school and college students. Members of the Department are involved in an extensive programme of radio/TV appearances and science commentaries in the popular press. This is important, because Genetics impacts so much on everyone’s lives and has such broad applications.  

 

The Department of Genetics lies at the heart of a much wider network of scientists in the University who use genetics in a wide range of biological and medical research. We have recently established an Institute of Genetics here at the University to promote interaction and provide a network structure to strengthen our already formidable record of genetic research.

 

At the heart of modern biology, genetics impacts on many aspects of human health, welfare and daily lives and is clearly a priority for government and industry alike.   Our reputation is internationally acclaimed, and we see the Institute as an opportunity to open up new initiatives, attract increased funding and collaborations and to enhance the education and training we can offer the next generation of scientists.”

 

Some of the key areas of our research which impact on the health and welfare of society are expanded below.

 

The Chernobyl Legacy

 

In 1986 the nuclear accident at Chernobyl in the Ukraine contaminated the surrounding regions – and beyond - with radiation. The world waited with baited breath to see what the long-term effects of this would be. Geneticists at the University of Leicester began to investigate, and their work continues today.

               

In the knowledge that predicting the genetic consequences for humans of exposure to ionising radiation and chemical mutagens has become one of the most important issues of human genetics, Dr Yuri E Dubrova and Professor Sir Alec Jeffreys developed a new system for monitoring radiation-induced mutation in the germline of mammals. 

 

Tests have shown for the first time that those families from Belarus and Ukraine who were exposed to the Chernobyl radioactive contamination, and families from Kazakhstan exposed to the fallout from nuclear weapon tests, are significantly more likely to pass on mutations to their children. Among the wider applications of this research is the suggestion that their methods can also be used where there has been exposure to chemicals.

 

Their research continues, including looking at the genetic risks of ionising radiation for humans from accidental or occupational exposure and radiotherapy. In the long term the hope is to be able to develop recommendations for establishing a mutagen-free environment.

 

Re-setting the Biological Clock

 

The major industrial accidents of the last century, Chernobyl, Three-Mile-Island and Bhopal, were all caused by human error during shift work – 25 per cent of the workforce in the industrial world works shifts.

 

In addition, sleep problems, particularly in older people, can lead to depression, and anyone who flies across time zones understands the misery of jet lag.

 

On the face of it there may not appear to be a link between all this and the fruitfly but, as research by Professor C P Kyriacou at the University of Leicester Department of Genetics and Dr E Rosato in the Department of Biology shows, genetically speaking, humans and fruitflies are more alike than you might imagine.

 

The discovery of clock genes in the fruitfly, Drosophila, led to the identification of these same genes in humans, and in turn to the development of therapies that attempt to alleviate some of the medical problems associated with issues such as shift work, jet lag and insomnia.

                       

Some therapies already available include the use of melatonin for jet-lag and bright light to counteract Seasonal Affective Disorder (SAD). The importance of this research will increase in the future, with the growth of airline – and even space – travel and the acceptance of the 24-hour society.

 

Like Father, Like Son

 

As part of his research into Y chromosomes, human evolution and genealogy, Dr Mark Jobling, Lecturer and Wellcome Trust Senior Research Fellow in the University of Leicester Department of Genetics, is exploring the relationship between surnames and genetic structure.

 

Most people get their surnames from their father, and all males get a section of their genetic material (DNA) from their father, too. This is the Y chromosome, responsible for making males. Females have two X chromosomes, while males have one X and one Y.

 

Dr Jobling’s research aims to find out how different kinds of Y chromosomes relate to different surnames – whether all males who share a particular surname also share a kind of Y chromosome and therefore a common ancestor, and what can be learned from this about the history of Britain.

 

This is not only of interest to those tracing their family trees, but it also has forensic implications. There may come a day when samples taken from a crime scene could suggest a surname. In the field of medicine, too, surnames are often used to look at population structure and predict the risk of diseases such as cancers and cardiovascular disease.

 

Dr Jobling’s work may be able to put these studies on a sounder scientific basis by using modern molecular genetic methods to test some of the underlying assumptions.

 

Hopes for Medical Breakthrough

 

Significant progress in identifying the genetic structure of diseases, including studies by Professor Richard Trembath at the University of Leicester, has generated new ways of identifying people who are ‘at risk’, as well as potential targets for therapeutic developments.  

           

Over the past three years Professor Trembath and others in the field have identified genes responsible for a range of medical conditions. While not all of these will lead to ‘miracle cures’, they do promise significant opportunities for families carrying genetic disorders.

 

One such condition, primary pulmonary hypertension (PPH) is a devastating condition causing a substantial increase in the blood pressure in the supply to the lungs. The consequences are a markedly reduced capacity for the transfer of oxygen to supply the body’s needs, together with substantial strain on the right side of the heart, typically leading to heart failure and early death. It is a sobering thought that one of the mainstays of treatment includes heart-lung transplantation.

 

A proportion of patients have a family history of the disease and Professor Trembath’s group working in Department of Genetics recently identified the gene responsible. Demand for tests for this gene has been high. Even though there is as yet no treatment for the condition, the knowledge that they have a predisposition to it helps people to normalise their lives.

 

Using Yeast as a Model and Tool

 

The Department is also at the forefront of research using the brewer’s yeast Saccharomyces cerevisiae, the model of choice for basic cellular processes. The sequencing of the genome of yeast and was the test case for the sequencing centres completing the human genome project. Members of the Department were involved in that project and continue to be involved in the worldwide efforts of determining gene function in this post-genomic era. For example,using the powerful technologies of modern yeast molecular genetics we are investigating cellular pathways leading to the production of essential B-vitamins. It may become possible to produce B-vitamins for food and therapeutic use by natural fermentation routes rather than the current chemical synthesis.

 

Yeast is also turning out to be an excellent model for some of the most important pathogens affecting human society to-day. The department is involved in applying those lessons learned in yeast to the fungal pathogen Candida albicans ( a major source of serious infection particularly in immune compromised individuals) and Pnuemocystis carinii ( the major cause of pneumonia in AIDs patients). 


Improving the Quality of Life

 

Professor Ed Louis, Professor of Genetics and Co-ordinator of the newly-established University of Leicester Institute of Genetics, sees a broad sweep of medical conditions that may be better understood in the future, using genetic techniques.  Initial benefits may simply be that we gain a better understanding of  specific diseases such as the biochemical defect involved in genetically predisposed forms of cancer.

 

Looking further ahead, cancer drugs will be tested in combination with anti-telomerase therapies (telomerase is an activity within cells which gives cancer cells their immortality) ultimately leading, perhaps, to the first ‘magic bullet’ against the most resistant tumours.

 

New prophylactic and therapeutic drugs will be monitored for a variety of diseases – many of which are developing resistance to current drugs. As new therapies are developed and diseases become increasingly rare the human life span will increase, and while Professor Louis does not expect people to live beyond 120 years, he does hope that more people will approach that age enjoying a high quality of life!

 

War Against Food Poisoning

 

The microbial safety of food is an issue continually in the public gaze. Now, using genomic techniques it will be possible to design approaches to reduce the incidence of food-borne disease.

 

Some of the most familiar such diseases include Salmonella and E.coli 0157, and Cryptosporidium of summer floods fame. Others are less well-known, though they may be much more frequent, most notable is Campylobacter, the most common cause of food poisoning across the world. Campylobacter lurks harmlessly in the intestine of most birds and animals, and when meat is undercooked or foodstuffs in fridges are cross-contaminated, it enters the human intestine causing cramps and diarrhoea.

 

Professor Julian Ketley, Professor of Bacterial Genetics at the University of Leicester, is using the whole genome to look for clues in the genetic structure of campylobacters to determine how the disease is caused. Some questions he is asking include: What happens if we stop a particular gene working? When exactly are the Campylobacters’ genes switched on and in response to what?

 

He believes that ending the misery and negative economic impact of diarrhoea is one important scientific goal for genome research on Campylobacter.  “For those thousands of us doing battle with Campylobacter,” he says, “exciting new developments in genetics will speed us towards winning the war.” 

 

November 2002

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Last updated: 18 November 2002 10:55
Created by: Rachel Tunstall

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