Winter 2005 Newsletter

Professor George Duncan receives the Monica Lumsden Award from Trustee Reg Buckley

Monica Lumsden Award

It was Sir Peter Medawar, winner of a Nobel Prize for his work on human tissue graft rejection, who pointed out that ‘Science is the Art of the possible’. Good science is in fact only possible if there are several essential ingredients in place at the same time. There must be intelligent and hard working people to carry out the project, good facilities and an encouraging environment for them to prosper in and a worthwhile aim to inspire them. However, to make the possible also happen there must be adequate funding and resources available and this is what The Monica Lumsden Award will provide for The Humane Research Laboratory at the University of East Anglia. There is certainly an outstanding group of people there led by Professor George Duncan, a leading International authority on Cataract and other Eye Diseases. He is ably assisted by Dr Michael Wormstone, the Trust’s first PhD student, and now THRT Lecturer at UEA and also by Dr Julie Sanderson, lecturer in the School of Pharmacy who is fast building a reputation in the glaucoma field. The THRT laboratory is also embedded in an excellent research environment. The School of Biological Sciences was rated a top Grade 5 at a recent National Research Assessment Exercise and is supremely well equipped to carry out modern cell and molecular studies on a range of human diseases. The Eye group have quite unparalleled access to donor eye tissue, essential for their work through Mrs Pamela Keeley at the neighbouring East Anglian Eye Bank. The Eye Group also have the active participation of a number of Eye Consultants from the Norfolk and Norwich University Hospital. Most importantly the Group also comprises a number of outstanding younger scientists: the Post-doctoral researchers, the bed-rock of any laboratory, Drs Lixin Wang, Jeremy Rhodes and Julie Eldred and the enthusiastic and talented PhD students Lucy Dawes, Vicki Tovell and Lisa Hodgkinson. 

On being presented with The Monica Lumsden Award of £100,000 on behalf of the THRT Laboratory at UEA, Professor Duncan said he was very grateful for the Trust's continuing support. "Science is only possible if there are good people to do the work and good, long-term finance to underpin that work," he said. "I have been very lucky in both respects here. Much of this most generous award will be used to buy cutting-edge equipment for the team."     

Professor George Duncan - University of East Anglia

Human Cells to Investigate Fat Metabolism

Professor Keith Frayn University of Oxford

Phd Student Jenny Collins and Professor Keith Frayn

Excess carbohydrate in the diet can be converted into fat and stored.  This process is called de novo lipogenesis (literally, synthesis of new fat).  There has been great interest in this process from both dieters and scientists.  For scientists, interest has centred on the last step in the metabolic pathway in which saturated fat, made from glucose, is converted to unsaturated fat.  This process is called desaturation.  It is well known that saturated fat has adverse effects on health, leading to increased risk of diabetes and of heart disease, whereas unsaturated fat tends to protect against these conditions.  The current intense interest in de novo lipogenesis and desaturation stems from observations in a genetically-altered mouse, in which the key enzyme for desaturation of saturated fats was inactivated (‘knocked out’).  Quite contrary to expectations, mice deficient in desaturation were healthier than normal mice: they resisted becoming fat when fed a high-energy diet and their tissues were more sensitive to insulin, a sign of protection against diabetes.

It is very important that we try to understand the relevance of these observations to humans.  There are several important differences in fat metabolism between mice and humans.  We have some preliminary evidence in humans that when we improve sensitivity to insulin (using one of a new generation of anti-diabetic drugs) this is associated with an increase in the activity of fat desaturation, making it very likely that men and mice differ fundamentally.

In order to study this process in more detail, we need to develop a cellular model.  Over the past few months, with the help of other scientists expert in growing cells in dishes (‘tissue culture’), we have begun to establish a method by which we can take human fat cells and grow them in dishes, enabling us to perform detailed cellular and molecular studies of de novo lipogenesis and fat desaturation.  We have some exciting preliminary data that show that we can measure these processes in human cells and that the activity of the gene that controls desaturation (called SCD) is regulated by the amount of saturated fat present in the cells.

The Humane Research Trust have now generously funded a PhD studentship for Jenny Collins to follow up these observations.  Jenny will first refine the cellular model.  Then she will investigate whether de novo lipogenesis is an important pathway in human fat cells under various conditions.  (Previously it has been studied almost entirely in rats and mice, and as indicated above there are good reasons for thinking that human fat cells may be quite different in this respect.)  Jenny will next investigate the molecular mechanisms involved in regulating the genes that control de novo lipogenesis and desaturation.  Finally Jenny will investigate whether the process of de novo lipogenesis has a role in fat cells in regulating the amount of fat that they are able to burn (oxidise).  This last aspect is completely novel and would be of great interest, potentially in the longer term leading to ways of burning off excess body fat.

The funding will pay for Jenny’s studentship costs and will buy us a new microscope to replace the elderly one we use at present.  We hope the results will show the feasibility of conducting detailed studies of these processes in human cells.  We expect to show that there are many fundamental differences in fat metabolism in human cells compared with rodent cells.

Prized Posters

We are all aware of the impact of posters on hoardings in our every day life persuading us to buy fizzy drinks, new fast cars and to visit fast food outlets. Their aim is to catch our attention and at the same time persuade us of the value of something. Exactly the same purpose, but of much greater ultimate value, underlies the function of posters at scientific meetings; they are a visual means of getting across an important message to a busy audience. At large International Conferences there may be as many as 1000 posters on display on the same day and usually about 100 of these are directly relevant to a particular area of research. It is vitally important to design a poster that is eye-catching, that is easy and interesting to read and delivers a valuable and convincing message. Posters have become such an important part of Conference Meetings that coveted Prizes are awarded for the best efforts.

It is heartening to see that posters designed by Humane Trust Researchers have been regularly winning poster prizes over the years. The first was probably won by Dr Julia Marcantonio from the Norwich Eye Group in 1980 at an Eye Research Meeting in Parma. The poster dealt with a new means of identifying molecular changes in human cataracts by simply noting the colour of the lens and measuring the sodium and calcium content. It involved a novel means of taking colour photographs of lenses within the patient’s eye before surgery. Interestingly, and 25 years later, Lixin Wang working at the Humane Research Trust Laboratory in Norwich won a prize for his poster identifying important roles for the amino acid tyrosine and the novel Sigma Receptor in the production of lens colour. Humane Research Trust student Anthony Oliver working with Drs Ian and Lynne Hampson in Manchester recently won a prestigious Keystone scholarship for his poster on the role of the Tip-1 protein in Cancer Chemotherapy. This was highlighted in the Spring 2005 Newsletter. Former THRT student (and now THRT Lecturer) Michael Wormstone won two coveted AER/Chauvin prizes in successive years at Eye Research conferences in Montpellier for his work on the Mechanisms of Posterior Capsule Opacification. Michael’s Poster Production expertise has also been enlisted to win 2 other prizes with other UEA groups in the area of Cancer Research.

Posters provide an excellent opportunity to meet fellow scientists and to have one’s work scrutinised at close quarters. During a poster day, three to four hours can be spent in ceaseless discussion. This is a very tiring, but ultimately rewarding experience, especially for younger scientists as it gives ample opportunity to meet like-minded colleagues and indeed to form the life-long collaborative links that are so important in driving research forward with shared resources.

Professor George Duncan – University of East Anglia