Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

Funded PhD: Dr Annie Curtis - the role of the molecular clock in controlling metabolism within innate immune cells - circadian immunometabolism

The purpose of the PhD is to uncover metabolic signals that are regulated by the molecular clock and alter the inflammatory response. This project will impact our understanding of how we treat inflammatory diseases but also the time-of-day we treat inflammatory diseases. The project will utilise state-of-the-art techniques such as metabolic profiling, proteomics, RNA sequencing, flow cytometry, cellular imaging and electron microscopy. This project will also benefit from in vivo models of molecular clock ablation and of clock disruption.

Lab overview

The Curtis Clock Lab investigates how the body clock controls the innate immune system. The body clock is the timing mechanism within our cells that ensures that certain physiologies or functions occur at the appropriate time of day (termed circadian rhythms). We have a particular interest in how the inflammatory response from macrophages and dendritic cells is under the control of the body clock. Modern life in terms of our erratic sleeping and eating patterns and shiftwork is causing disruption of our body clocks, and this is leading to dysregulated inflammation and an epidemic of chronic inflammatory conditions.

We believe that dysregulation of our innate immune clock is a key contributing factor to this dysregulated inflammation. The Curtis Lab has previously discovered a role for the pro-inflammatory microRNA MiR-155 in controlling the molecular clock in macrophages (1) and have uncovered that the macrophage molecular clock restrains asthma (2) and multiple sclerosis (3).  Our work has implications on how we treat inflammatory diseases but also when we treat inflammatory diseases. The Curtis Lab has between 7-8 staff and students at any one time and promotes and fosters a culture of collaboration, diversity, equality and inclusion. 

Project description

Immunometabolism is an emerging hot topic in immunology, in which the type of metabolic pathways performed within a cell 'programs' the type of immune response. 

However, the role of the molecular clock in controlling metabolism within innate immune cell is not known, and the consequences in terms of immune function have yet to be explored. The Curtis laboratory is taking a leading position in this new frontier area of clock-controlled immunometabolism which we have termed circadian immunometabolism (4). 

  1. Curtis, A. M., Fagundes, C. T., Yang, G., Palsson-McDermott, E. M., Wochal, P., McGettrick, A. F., Foley, N. H., Early, J. O., Chen, L., Zhang, H., Xue, C., Geiger, S. S., Hokamp, K., Reilly, M. P., Coogan, A. N., Vigorito, E., FitzGerald, G. A., and O'Neill, L. A. (2015) Circadian control of innate immunity in macrophages by miR-155 targeting Bmal1. Proc Natl Acad Sci U S A 112, 7231-7236
  2. Zaslona, Z., Case, S., Early, J. O., Lalor, S. J., McLoughlin, R. M., Curtis, A. M., and O'Neill, L. A. J. (2017) The circadian protein BMAL1 in myeloid cells is a negative regulator of allergic asthma. American journal of physiology. Lung cellular and molecular physiology 312, L855-L860
  3. Sutton, C. E., Finlay, C. M., Raverdeau, M., Early, J. O., DeCourcey, J., Zaslona, Z., O'Neill, L. A. J., Mills, K. H. G., and Curtis, A. M. (2017) Loss of the molecular clock in myeloid cells exacerbates T cell-mediated CNS autoimmune disease. Nat Commun 8, 1923
  4. Early, J. O., and Curtis, A. M. (2016) Immunometabolism: Is it under the eye of the clock? Seminars in immunology 28, 478-490

Specification

Qualifications:

  • Upper second class (2.1) honours degree or higher in biological sciences or related subject 
  • For candidates who do not speak English as their first language, IELTS or equivalent English language test scores of at least 6.5 is required 
Knowledge and experience(Essential):
  • A passion for fundamental scientific discovery 
  • A keen interest in immunology and in the underlying basis of inflammatory conditions, 
such as Arthritis, Diabetes, Obesity, Cardiovascular Disease and Cancer 

  • Dynamic, highly motivated and results driven 
  • Proven ability to work independently and as an effective and dynamic team member 
  • Ability to communicate effectively 
  • Strong organisational skills with the ability to produce results and prioritise tasks 

Application process and scholarship details

Please apply here with an up-to-date CV, a 500-word statement outlining your interest in and suitability for the position, and contact details of two referees.

  • Application deadline: Friday, 15 June 2018 at 5pm.
  • Interview date: July 2018
  • Start date: 1 October 2018
  • Department: Department of Molecular and Cellular Therapeutics 
  • Location: RCSI, 123 St Stephens Green, Dublin 2
  • Tenure: 48 months
  • Stipend: 18,000 per annum 

Mentors Dr Annie Curtis