Vitamins, minerals and micronutrients are naturally occurring compounds with essential biological activities. Although their consumption does not provide any direct calorific return—as would be the case for macronutrients i.e. protein, fat, carbohydrate—their deficiency can have a major impact on human health through their effect on protein production. Two examples of this are selenium and queuine (see below) which are critical micronutrients for optimal protein synthesis.
For the past decade, our laboratory has been pursuing a largely unexplored avenue of research, working on the queuine micronutrient. This molecule is made exclusively by bacteria but surprisingly is salvaged by plants and animals, including humans, leading to improved accuracy of protein translation. Our efforts succeeded in identifying the mechanism that mammals use to obtain queuine from the diet and we have made substantial progress in understanding queuine’s physiological role. Part of the attraction of working in the micronutrient field is the breath of physiological effects that these often-overlooked molecules can have in disease, human health and aging.
Sir James Black, Scottish physician, pharmacologist and 1988 winner of the Nobel Prize in Physiology and Medicine, once famously stated that “The most fruitful basis for the discovery of a new drug is to start with an old drug”. In this vein of thought, our group in collaboration with colleagues in Chemistry, Dr. Mike Southern and Prof. Stephen Connon, have been developing analogues of queuine to interrogate the possibility of using such compounds to treat disease. We could show that queuine mimetics can drastically reverse the clinical disease process (i.e. paralysis and immune activity in the brain) that are associated with the animal model of Multiple Sclerosis. Based on these findings, my colleagues and I have co-founded a university spin-out company called Azadyne that is now developing queuine-based therapeutics for the treatment of autoimmune disease.
Arguably, above any other aspect of human physiology, the ability to generate offspring is paramount. There is now a growing awareness, as highlighted extensively in the media, that fertility in men is dropping drastically in the Western world. Sperm counts have more than halved in the past 40 years and it is estimated that the levels are continuing to fall by an average of 1.4% per year. Although there is no impending threat of human extinction, the impact can be tragic for those couples trying to conceive. Surprisingly, the underlying cause for this drop in fertility remains uncertain. Based on our laboratory’s experience in fertility and transgenic technologies (see below) we have ongoing investigations on the use of micronutrients in male infertility and the study of RNA receptors for the treatment of male infertility.
With over 25 years’ experience in transgenic technologies, our research group established the only transgenic facility on the island of Ireland (www.transgenics.ie) a little over 10 years ago. Presently, the transgenic facility offers a range of services including, rederivation, IVF, sperm and egg cryopreservation, dry-shipping and cold-shipping of germplasm and CRISPR/Cas9 RNA gene-editing technology to manipulate the mouse genome. Our transgenic facility has carried out many hundreds of vital transgenic tasks for researchers in Trinity College and other universities nationally. As always, we are delighted to discuss new projects and provide advice to researchers on the optimal transgenic methods to address individual research questions.
Our capabilities in animal-based technologies and disease models has led to many fruitful academic and commercial collaborations. We are delighted to be working with colleagues in the UK, Europe and Japan on the BIND project (https://bindproject.eu/), which is led by the esteemed neurologist Prof. Francesco Muntoni, Great Ormond Street Hospital. The BIND project is the first project of its scale to characterise the brain involvement in Duchenne and Becker Muscular Dystrophy (DMD and BMD) and will examine various RNA-based modalities to provide improved quality of like for sufferers of this disease. The Irish component of this EU-funded project involves us working in close collaboration with Transpharmation Ireland a recognized world leader in behavioural and biomarker research applied to psychiatric and neurodegenerative disorders.
Naturally, teaching has been an important part of my academic career. In 2006, I established a new degree moderatorship in Molecular Medicine, which is consistently among the top 3 most popular science degree options in Trinity College. Furthermore, I was the Molecular Medicine course director for an accumulative term of 14 years; 6 and 8 years as the Junior and Senior Sophister co-ordinator, respectively. During my time as the Director of Undergraduate Teaching & Learning I re-introduced and redesigned the moderatorship in Biochemistry and sourced the original funding that set in place a Virtual Learning Environment (VLE) for undergraduate practical teaching. The topics of my undergraduate teaching portfolio vary across biochemistry, genetics, molecular, cellular and whole animal research and include courses on Stem Cells, Animal Transgenics, Drug Development, Cancer & Metastasis, The Cell Cycle, Molecular Basis of Transcription & Translation and The Chemical Biology of Life.
Imagination is more important than knowledge. Albert Einstein