The VitDAL research programme, led by Professor Richard Mellanby, explores the relationship between vitamin D, inflammation and health outcomes in companion, farm and wild animals. These studies run alongside mechanistic investigations in murine experimental disease models. This diverse, multi-species approach allows the lab to address key research questions on the biology of vitamin D which would not be possible using a single species system.
The VitDAL research programme has two key themes:
- Investigations into the immunomodulatory properties of vitamin D
- Investigations into the non-skeletal health benefits of vitamin D in veterinary species
Investigations into the immunomodulatory properties of vitamin D
This programme of work focuses on how investigating how vitamin D modulates the host immune response. The VitDAL has demonstrated that vitamin D supplementation ameliorates the development of experimental autoimmune encephalomyelitis (EAE) when induced by the administration of an adjuvant and myelin autoantigens. In contrast, we have found that administration of vitamin D does not alter the development of active EAE which arises following the administration of ex-vivo activated myelin responsive T cells. This finding has anchored the lab’s long standing research interest on understanding the effects of vitamin D on myeloid cell biology. Our research has shown that vitamin D modulates expression of inhibitory molecules, cytokines and chemokine receptor on dendritic cells generated in vitro. The functional relevancy of these protein changes have been probed by gene silencing siRNA techniques, over-expression vectors and a wide range of in vitro and in vivo assays which we have developed over the past decade, including a novel model of EAE in which central nervous system autoimmunity develops following the transfer of naïve auto-antigen responsive T cells and APCs loaded with a relevant peptide. This programme of work has been supported by three consecutive Wellcome Trust Fellowship Awards and builds on the Mellanby lab’s previous published research into regulatory T cell biology and the mechanism of T cell tolerance.
Investigations into the non-skeletal health benefits of vitamin D in veterinary species
The VitDAL also lead population-based epidemiological studies which are examining the relationship between vitamin D, inflammation and health outcomes in numerous animal populations. We are studying vitamin D homeostasis in several well-phenotyped sheep flocks and cattle herds based in the UK and overseas from which longitudinal vitamin D metabolite data is available. I am also studying vitamin D metabolism in wild animals, notably an unmanaged Soay sheep flock resident on St Kilda. This programme of work has recently demonstrated a relationship between vitamin D status and fecundity which is the first study to link vitamin D and ecological fitness in wild animals.
The VitDAL run a parallel translational clinical vitamin D research programme which studies spontaneous vitamin D metabolism disorders in client-owned companion animals. This work has resulted in the clinical validation of parathyroid hormone related protein and vitamin D metabolite assays and led to the description of several novel calcium homeostasis disorders in dogs. We have described a novel syndrome of hypovitaminosis D in dogs with inflammatory bowel disease (IBD). Follow-up studies have demonstrated an association with low vitamin D status and gastrointestinal and systemic inflammation and, importantly, with a poor clinical outcome. This programme of work has expanded into a broader investigation of the relationship between vitamin D biology and a wide range of infectious, neoplastic and allergic disorders in companion animals. A key finding of this work has been the demonstration that low vitamin D status is highly predictive of all-cause mortality in hospitalised cats. In addition, we have demonstrated that steroid resistance in canine atopic dermatitis is associated with hypovitaminosis D.
The VitDAL research programmes works closely with collaborators across the world. We welcome enquiries from both veterinarians and non-veterinarians who are interested in discussing potential collaborations.
We also welcome enquiries from students interested in undertaking a PhD and postdoctoral scientists interested in developing fellowship applications. If you are keen to discuss opportunities in the VitDAL lab please email Richard.Mellanby@ed.ac.uk