Immunometabolism, Is it under the eye of the clock

Annie Curtis reports

Our Immune-clock laboratory has a real interest in metabolism and how alterations in metabolic pathways termed “metabolic reprogramming” can shape the type of immune response. This area called “Immunometabolism” has exploded in the last 5 years, and the implications are massive. It appears that macrophages use one metabolic pathway to become highly proinflammatory and another metabolic pathway to resolve inflammation and promote wound healing.  So why is our laboratory so interested in this? Well, if you think about daily changes in our environment, the two biggest are the sleep/wake cycle and the other is feeding/fasting. It is now clear that clocks in metabolic tissues like the liver/pancreas/adipose tissue prepare the body to deal with this daily rhythm in feeding/fasting. Based on this, our interest is to figure out if the clock within macrophages is somehow altering its metabolism over the course of the day and is that leading to changes in macrophage function, particularly the inflammatory response.

Jamie Early, my PhD student

Jamie Early, my PhD who “lives” in Prof. Luke O’Neills laboratory at TCD and I were invited to submit this first ever review on circadian immunometabolism, and you can find it here.

Additional reading

  1. Early JO, Curtis AM Immunometabolism: Is it under the eye of the clock?Semin Immunol. 2016 Oct;28(5):478-490

Follow me on Twitter @curtisannie

Using genotype data to infer population structure and history

MCT Research Talk – 12th December

The Human Genetic Variation Research Group 

The Monday 12th December MCT Seminar Series will feature presentations from Amy Cole and Edmund Gilbert, of the Human Genetic Variation Research Group at RCSI. Led by Prof. Gianpiero Cavalleri, this research group studies large genetic datasets to investigate population structure, natural selection and the genetic basis of human disease.

Andean native in a small village on the outskirts of Cuzco

Amy Cole’s research focuses on identifying adaptive genetic variants in high altitude populations.  There are more than 140 million people living at high altitude who are exposed to two primary environmental extremes; hypobaric hypoxia and cold. At altitudes >2500 m individuals have between 11-14% effective oxygen availability, instead of the 21% available at sea level. Previous studies have identified genetic signals of selection across the genome, which have facilitated an adaptive phenotype for survival in this hypoxic environment.  Studying these indigenous high altitude populations will enable us to shed light on genes and molecular mechanisms involved in the response to hypoxia. This insight can help shed light on a number of illnesses associated with hypoxic states in low altitude populations, such as pneumonia, chronic obstructive pulmonary disease, asthma and cancer.

Research group en route to Cerro de Pasco

Today Amy presented research on a whole genome sequencing project on native high altitude Quechua individuals, recruited from the city of Cerro de Pasco, Peru, during a field trip in 2015.  Amy recently completed a three-month lab placement at MD Anderson Cancer Center with Professor Chad Huff’s research group. Here Amy performed a number of computational analyses to identify regions of the genome that are under selection in this cohort.

Edmund Gilbert’s research involves investigating the genetic structure and diversity found within the Irish. As an island population on the west of Europe, the Irish population is, from the genetic perspective, relatively homogenous compared to populations of the European mainland. As a results of this elevated homogeneity, the Irish population is well suited to studies of genetic disease. Such studies have recently shifted focus towards rare variants, which are more geographically stratified than more common variants. Therefore understanding the population structure within Ireland is key for the optimal design of genetic disease causing rare variant identification within the Irish.

Today Edmund will be presenting research investigating the extent of fine-scale population structure found within Ireland. He has been using SNP-array genotype data from the genetic ancestry DNA cohort called the “Irish DNA Atlas”. The Atlas is a cohort of individuals with Irish ancestry from three generations ago who have all eight of their great-grandparents born within 50 km. Edmund will be presenting analysis based on the suite of software known as fineStructure; investigating both fine-scale structure as well as the genetic ancestry of this structure.

Amy Cole, Edmund Gilbert, Gianpiero Cavalleri

HEAD OF DEPARTMENT’S WELCOME

 

Prof. Tracy Robson Head of Molecular & Cellular Therapeutics (MCT), Royal College of Surgeons in Ireland
Prof. Tracy Robson Head of Molecular & Cellular Therapeutics (MCT), Royal College of Surgeons in Ireland

It gives me great pleasure to welcome you to MCT’s blog page. Our department is based within the Royal College of Surgeon’s in Ireland (RCSI) situated on Dublin’s beautiful St Stephen’s Green.  This was one of the initial attractions for my move to Dublin from Queen’s University Belfast in Aug 2016, in addition to the vibrant and innovative environment that RCSI provides, through its achievements in education and research.

Our research focuses on understanding the molecular basis of disease in order to develop and apply our findings to the identification of biomarkers and new drug targets. Our aim is to improve the diagnosis, treatment and, ultimately, prevention of disease; enabling MCT to be at the forefront of personalized medicine. With newly renovated state-of-the-art facilities, strong links with Beaumont Hospital, our clinician-scientist teams are leading therapeutic and biomarker discovery in the areas of autoimmune and inflammatory disease, cancer, cardiovascular disease, infection, platelet biology and neurological and psychiatric disease. This is facilitated by strong collaboration with industry allowing us to translate our findings appropriately, revolutionizing healthcare through discoveries and innovations that improve people’s lives.

I hope that you enjoy reading our blog page which seeks to capture the dynamic nature of the teaching and research environment within MCT and pays testimony to the significant accomplishments of our all of our staff and students.  I hope that we can inspire you ………

Tracy Robson