ULCaN Seminar Series
Time and Date
Friday, 5th March 2021, 1pm
(via MS Teams)
Microsoft Teams meeting
Join on your computer or mobile app
Speaker: Dr.Kieran McGourty
University of Limerick
"The Molecular Basis of pro-Survival Signalling during Cell Quiescence"
Controlled cell division is critical for tissue homeostasis and maintenance. A cell must recognise specific signals from its microenvironment to determine whether it should divide or maintain a resting state [1, 2, 3]. Quiescence (also named ‘G0’) is the state in which cells are not dividing but retain the ability to restart their proliferation upon stimulation. Many cells, including stem cells, require the ability to persist in a quiescent state and to be able re-enter the cell cycle as required, such as during wound healing, growth or as part of normal tissue turnover. Thus, the ability of cells to alternate between proliferation and quiescence is crucial for renewal, organism development, maintenance and response to life-threatening challenges. However, our understanding of the molecular mechanisms that control quiescence is limited. This project identifies signal transduction events arising from the microenvironment that support the entry of cells into quiescence and their long-term survival.
Here I will speak to how used phosphoproteomic SILAC mass spectrometry, meta-analysis and machine learning classification and high throughput microscopy screens to identify a panel of surface and extracellular matrix proteins that are characteristic of G0 and are suitable as discriminators of quiescence in both normal, primary cells or in the intestinal stem cell niche. In addition, phosphoproteomic data were used to evaluate the signalling landscape of quiescent cells yielding insight into the survival mechanisms of these cells.
Importantly, a specific intracellular signalling landscape that restricts key signalling complexes to the cytosol during quiescence was identified. Specific perturbation of this signalling profile, induced apoptosis in quiescent cells, showing an activity requirement for survival of quiescent cells. Consistently, exit from the cell cycle, G0 surface marker expression, enhanced cytosolic signalling activity was induced when both primary and normal cells were cultured on selected ECM substrates. These cells displayed similar survival characteristics as G0 cells. Lastly, evidence of similar regulation was confirmed in vivo in the intestine in quiescent intestinal stem cells.
This research provides important insight of the signalling regulation and proteomic landscape of quiescence. As such, it contributes to our understanding of how cell homeostasis is regulated during development, healthy adult life and ageing.
Dr. Kieran McGourty is currently a lecturer in the Chemical Sciences department at the University of Limerick, Ireland. He obtained a Bachelor of Science in industrial biochemistry in the University of Limerick, where he worked with Dr. Jakki Cooney and Dr. Todd Kagawa. In 2006, motivated by these experiences, he went on to attain a Wellcome Trust funded PhD, working with Prof. David Holden FRS, Imperial College London to study the molecular basis of infection. During this time, Dr McGourty published several high impact papers on the intracellular interaction of Salmonella Typhimurium with the host before changing field from cellular microbiology to cell biology. He took a post-doctoral research position in 2012 with Dr. Emmanuel Boucrot at University College London (UCL), with a primary research focus on the cell cycle and extracellular matrix (ECM) biology. His work here resulted in an extensive study into how ECM interaction evoke specific intracellular signalling profiles in quiescent cells.
Kieran’s research at UL continued investigation into cell regulation and aims to understand the signals that govern cell behaviour, especially the intestinal, muscular and epidermal niche. He employs a number of high-throughput techniques to achieve this including; transcriptomics, single cell multiomics, phosphoproteomics and high content imaging, in addition to standard biochemical techniques. Lastly, Kieran is a committee member of Matrix Biology Ireland and is a Local Ambassador for the Biochemical Society.