Dr Hadwen Trust Research Portfolio 2007

In addition to our on-going programme of research (see Porfolio 2006), in 2007 the Dr Hadwen Trust also began funding three major new projects to replace the use of genetically modified 'knockout' mice in experiments.

None of our research is on living animals or animal tissues, and all of it contributes to the replacement of animal experiments, whilst furthering research into human medical problems.

Replacing GM mice studies

The latest round of research grants awarded by the Dr Hadwen Trust, targets non-animal replacements in the world's fastest growing area of animal research – genetic experiments. We are funding ground-breaking research at King’s College London, the University of Manchester, the University of York and Queen Mary’s School of Medicine and Dentistry to target three key areas:

Replacing knockout mice in:

Gene function

Premature childbirth

Skin cancer

Recent years have seen a rapid rise in the number of genetically modified animals used in experiments. Over 950,000 procedures on transgenic animals were conducted in the UK alone in 2005, representing 33% of all procedures. An additional 288,000 procedures were conducted on animals with a harmful genetic defect. If nothing is done, this upward trend is almost certain to continue, having a dramatic impact on overall animal research numbers.

3-D human tissue structures with targeted gene disruptions:

Understanding gene function is vital in disease research. Experiments using genetically modified animals (particularly mice) with specific genes silenced or 'knocked out' are common but they don't represent a gold standard as there can be significant differences between the functions of equivalent genes in different species. The Dr Hadwen Trust's new project funding researchers at the University of York aims to develop methods to switch off genes in human tissues grown in the laboratory, to replace the use of knockout mice. These “knockout tissues”, with specific gene disruptions, will be created from donated adult stem cells from bone marrow, called mesenchymal stem cells (MSC). The cells will be grown in complex three-dimensional structures called MSC-spheroids and specific genes will be disrupted to investigate gene function. MSCs are rare adult stem cells that can develop into bone, cartilage, fat and possibly even liver, brain and heart muscle cells. This means that resulting human knockout tissues could have potential applications for researchers in a wider range of medical fields, particularly the study of arthritis and bone disease.

Human tissue model for premature birth research:

Abnormal labour, such as premature labour or failure to go into labour, affects some 30% of all pregnancies in the UK. Babies born at 23 weeks have just a 17% chance of survival. At present, relatively little is known about how the human womb works. Much research in this area has relied on animal experiments but important differences in the physiology of human pregnancy and that of other animals mean that results from these experiments have had little impact on our understanding of human pregnancy.

Our collaborative research at King's College, London and Manchester University will focus on the genes involved in the physiological control of labour. Strips of human uterus tissue, donated by pregnant women who have undergone caesarean section, will be studied in the test tube. The strips of uterus tissue maintain the ability to contract in the test tube for at least four days. The latest molecular biology tools will be used to silence the genes of interest.

No similar test tube model is known to currently exist and the development of the Dr Hadwen Trust's model will be of enormous benefit to researchers teasing out the role of specific proteins in the control of contractions so that new drug targets can be identified.

3D model of skin cancer:

Basal cell carcinoma (BCC) is responsible for three-quarters of all skin cancers in the West and is the most common form of human cancer. Basal cell carcinomas are tumours in the deepest layers of the skin. Growths usually occur on the face and neck, which are difficult areas to treat and require complicated surgery that can leave unsightly scarring. If caught early, BCC can be treated, but otherwise it can become dangerous.

At present there are no cell culture models of BCC and research is often carried out on mice genetically modified to develop tumours. Sometimes human skin cells may be implanted into mice with deficient immune systems in an attempt to model the disease. A single experiment can use as many as 400 mice; tumours can be large, aggressive and painful.

The Dr Hadwen Trust is funding leading cancer researchers at the Centre for Cutaneous Research at Queen Mary’s School of Medicine and Dentistry, London. Our research will attempt to develop the world's first multi-cellular model of BCC.