Many common psychiatric conditions are deeply connected on a genetic level

Global collaborations can help answer fundamental questions that are resistant even to national endeavours. Drs Mark McCormack and Christopher Whelan (MCT) and Professors Kieran Murphy (Psychiatry) and John Waddington (Emeritus, MCT) have participated in an important international study, the results of which have just been published in Science [2018 Jun 22;360(6395)] under the auspices of the Brainstorm Consortium. This landmark study, ‘Analysis of shared heritability in common disorders of the brain‘, analyses genetic data assembled globally from 265,218 patients having one of 25 neuropsychiatric disorders and 784,643 control participants, together with 1,191,588 individuals having 17 other, potentially relevant characteristics. Psychiatric disorders share an unexpected degree of common genetic risk: for example, genes associated with risk for schizophrenia are also associated, to varying extents, with significant risk for bipolar disorder, major depressive disorder, autism spectrum disorder, attention deficit/hyperactivity disorder, obsessive-compulsive disorder and anorexia nervosa; in contrast, neurological disorders such as epilepsy, stroke, Parkinson’s disease, migraine and multiple sclerosis appear more genetically distinct from one another. This highlights the importance of common genetic variation as a risk factor across psychiatric disorders.

https://www.irishtimes.com/news/health/many-psychiatric-disorders-have-common-genetic-links-major-study-1.3539455

 John L. Waddington PhD, DSc, FBPhS, MRIA
Professor Emeritus

 

Circadian Immunometabolism. What it is and why your immune system will not thank you for eating curry chips at 2am after the disco

MCT Research Seminar

The Curtis Clock laboratory has a real interest in metabolism, which is a really broad term and means different things to different people. We are interested in how different fuels (sugars , fats, proteins) are metabolised (broken down) within immune cells, and if this has an impact on how that immune cell functions. The key metabolic organelle within a cell is the mitochondria, that is where the breakdown parts of these fuels end up and are converted to energy (ATP). We are a Clock lab, so our raison d’etre (so to speak) is to unravel how different fuels are metabolised within immune cells at different times of day and how the mitochondria work at different times of day, and how that impacts the response of the immune cell at that time of day. This is what we now term “Circadian Immunometabolism”. This leads me on nicely to our title, before the age of electricity, our forefathers never ate in the middle of the night, we believe that our immune system becomes dysfunctional when it has to deal with food during a time when we now believe our immune system is undergoing repair and restoration. So to begin to get at these big questions, Mariana and George have two exciting projects ongoing. Mariana, who is a postdoc in the laboratory, will show how our mitochondria are changing over the course of the day in dendritic cells (these are cells of the innate immune system and are the ones that feed information to our adaptive immune system) (see Fig. 1). The title of her talk is

“Those mitochondria have got rhythms! Mitochondrial activity and antigen processing in dendritic cells is dependent on the molecular clock protein BMAL1”.

George, a PhD student in the lab, is dissecting down into the cells to figure out how the electron transport chain (the side of action for ATP synthesis) is controlled by the clock. The title of his talk is

“Metabolic pathways in a macrophage lacking a molecular clock”

Mitochondria have a very important role in cellular metabolism, their morphology is completely different during the day (elongated) (yellow) or during the night (fragmented) (blue) nucleus (gray)

Annie Curtis

More details of what we do can be found here: www.Curtisclocklab.com