Dr David Cole is Wellcome Trust Research Career Development Fellow at the Cardiff University School of Medicine.
From a young age I’ve had a natural affinity with science. Writing this article has led me to reflect on why this could be. My initial thought was that the Government must have pre-programmed my brain in an evil plot to create a society of people designed to solve problems through reasoned and logical thought, while playing Sudoku. My second thought was that perhaps science has been a good outlet for my overactive imagination.
For me, there is nothing more satisfying than imagining new and outlandish ways to investigate and understand biological systems. As an example, the imagination and ingenuity of Rosalind Franklin, James Watson and Francis Crick enabled the discovery of the structure of DNA in 1953. This underpinned countless imaginative and pioneering studies, which have resulted in a number of popular breakthroughs, including the cloning of Dolly the sheep and the human genome project.
Just as the structure of DNA allowed many scientists to understand and manipulate this fundamental molecule, my research is focused upon solving the structures of other molecules that allow the cells in our bodies to perform their important functions. In my laboratory, we are investigating a type of white blood cell that has a central role in our immune systems – the T-cell. The main function of the T-cell is to fight off infectious diseases caused by viruses and bacteria. T-cells also have an important role in killing cancer cells. T-cells are designed with an in-built safety mechanism, called self-tolerance, which normally stops them from accidentally reacting with healthy tissues. But when self-tolerance goes wrong, self-reactions can occur that are the root cause of auto-immune diseases, such as type 1 diabetes and multiple sclerosis. Because cancer cells are usually normal, healthy cells, which have malfunctioned in some way, self-tolerance can limit the ability of T-cells to react against, and kill, tumours.
However, there must be something inherently different about cancer cells, or why would they be cancerous? Many researchers have focused upon this question and have subsequently identified distinctive ‘cancer markers’ that some T-cells can recognise. Unfortunately, this recognition often results in only a weak T-cell immune response, and the large, rapidly dividing tumour mass is not destroyed.
To help to understand why this is, my laboratory has recently solved the structure of a T-cell protein molecule interacting with a skin cancer marker. This interaction has been shown to enable T-cells to kill skin cancer cells in the laboratory and in patients. Importantly, this line of work has revealed that T-cells have a very weak affinity for cancer markers, compared to viral or bacterial markers. This may explain why T-cells do not normally defend us against cancer. We hope to use our new discoveries and insights to design new strategies to manipulate T-cells so they have an artificially-enhanced ability to destroy tumours. In this way, T-cells could be used to naturally eradicate cancer cells without the harmful side-effects and risks associated with treatments like chemotherapy, radiotherapy and surgery.
It is great to be involved in such an important area of medical research in Wales. I hope to continue to improve the current understanding of the role T-cells play in human cancer. I envisage this research will lead to new therapies and diagnostics in the future.
To contact David please email firstname.lastname@example.org.
This article first appeared in the Western Mail‘s Health Wales supplement on the 22nd August 2011, as part of the Welsh Crucible series of research profiles.