For cells to produce protein, the DNA that contain our genes, is transcribed into sections of RNA, which are then translated into protein by the ribosome. Translation of proteins is terminated by a specific signal called a stop codon. Many cancers have acquired mutations in their genes which result in premature stop codons in RNA, meaning that the translated proteins are smaller than they should be and are often unable to function properly. Additionally, RNA containing a premature stop codon is recognised as abnormal and destroyed by a quality control process known as. Together, premature stop codons and nonsense-mediated decay results in the mutated protein not being made, which enables a cancer to grow out of control. Given that, according to the NHS, 1 in 2 people in the UK will develop some form of cancer during their lifetime, many of which are driven by premature stop codons in tumour suppressor genes, it is vital that new ways to overcome premature stop codons are developed and explored for their therapeutic potential. Tay Therapeutics (formerly In4Derm), a biotech company based in Dundee, have created highly active small molecules that overcome premature stop codons and restore the production of full-length, functional protein. This grant will fund proof-of-concept studies that this restoration of protein is enough to kill cancers. Ultimately, we envision this will lead to a powerful new way to treat a wide variety of cancers to the benefit of patients in the UK and around the world.

Eczema is the most common inflammatory skin disease, affecting 15-20% of children and up to 10% of adults, associated with substantial morbidity. It is a chronic relapsing condition, with varying frequency and duration of disease flares, in which the symptoms of itching, scratching and infection intensify. There have been few oral small molecule drug approvals for eczema in recent years, and current treatment options are sub-optimal due to lack of efficacy, side effects or route of administration. In4Derm has discovered a novel approach to the treatment of eczema that we believe will deliver the benefits of methotrexate, without the side effects. We will discover and validate biomarker models of inflammatory disease in mouse and human cells and tissues that can be used to predict drug effects in animal models of disease and in clinical trials. This will increase the chance of a drug successfully reaching the market.