MRC Centre for Inflammation Research
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Dr Sonja Vermeren

Sonja Vermeren's lab works on cross-talk P13K and small GTPase signaling and how this underpins neutrophil and endothelial cell function.

Dr Sonja Vermeren

Lecturer

  • MRC Centre for Inflammation Research
  • Research Theme: Immune Modulation and Regulation of Inflammation

Contact details

Group Members

  • Julia Chu - Postdoc
  • Barry McCormick - Postdoc
  • Ben Cathcart - PhD student (primary supervisor Dr Andrea Caporali)
  • Utsa Karmakar - PhD student
  • Melina Michael - PhD student

Background

Cellular signalling regulates diverse cellular responses including cell differentiation, growth, survival and migration, as well as specific functions of specialised cell types (eg neutrophil degranulation or production of reactive oxygen species). Depending on the situation their activation can result in different outputs. Examples for important signaling proteins include agonist-activated phosphoinositide 3-kinase (PI3K)  and small GTPases of the Ras superfamily (Ras, Rho, Arf etc). A typical cell has 25-50 different PI3K effectors, many of which are regulators of small GTPases, so-called guanine nucleotide exchange factors (GEFs) and GTPase activating proteins (GAPs) that aid GTPase cycling between the inactive, GDP-bound and the active, GTP-bound state. There are many small GTPase family members who in turn regulate a number of effectors. Interestingly, the number of GEFs and GAPs far exceeds that of small GTPases. My lab studies how the cross-talk between PI3K and small GTPases contributes to regulation of complex physiological processes such as neutrophil chemotaxis/recruitment.

Research Overview

We work specialised cell types, such as the neutrophil, the most abundant peripheral blood leukocyte in man. Neutrophils provide the first line of defense against infections. These short-lived, terminally differentiated cells leave the blood stream following activation to travel to sites of infection or sterile insult where they phagocytose and kill pathogens, releasing reactive oxygen species and cytotoxic enzymes and generate inflammation. We are also interested in endothelial cells, specialised cells that line blood vessels. Endothelial cells perform a barrier function and are being crossed by neutrophils (and other leukocytes). During inflammation the endothelial barrier becomes leaky, causing swelling. Both transendothelial migration and leakiness are complicated processes that are regulated by cross-talk between endothelial cell and leukocytes. We are interested in the signaling processes involved, focusing once more on PI3K and small GTPases. Much of our current work centres around ARAP3, a PI3K and Rap regulated GTPase activating protein for Rho and Arf family small GTPases. ARAP3 was one of many PI3K effectors identified in a screen for PI3K effectors from pig neutrophils. We already showed that ARAP3 regulates endothelial cell biology (angiogenesis). In the neutrophil, ARAP3 regulates chemotaxis and adhesion-dependent processes. We proposed that this is due to ARAP3-dependent modulation of the activity of leukocyte integrins. Our current questions are: How can the same enzymatic reaction lead to such different cellular read-outs in the two different cell types? What are the downstream effectors involved? How relevant are our observations for physiological situations in vivo?

Images of neutrophil chemotaxis (see details below image)
Neutrophils that did (left) or did not (right) contain ARAP3 were seeded onto glass and allowed to chemotax to a point source of chemoattractant. Cells were time-lapse imaged to visualize cell movement. In the stills shown, the movement of the individual cells was tracked. Control cells moved readily to the micropipette, whilst ARAP3-deficient did not. Stars show the original positions of the micropipette in the control field; this had to be moved to avoid the cells from crawling into the micropipette.

Biographical Profile

Vordiplom Biologie, Friedrich-Schiller-Universitaet Jena, Germany, 1993

MSc Biochemistry, University of Dundee, 1995

PhD, University of Cambridge, 1999

Post-doc and senior post-doc, MRC LMCB, London and The Babraham Institute, Cambridge, 1999-2005

Group leader, The Babraham Institute, Cambridge, 2006-2012

MRC/UoE CIR, University of Edinburgh, 2013 to date 

Honours and Awards

  • Boehringer Ingelheim Fellowship 1996-1999
  • Deutsche Forschungsgemeinschaft Research Fellowship 2001-2002
  • BBSRC David Phillips Fellowship 2006-2011
  • Chancellor's Fellowship 2013-2018

Alumni

  • Marta Canel (Postdoc, currently Postdoc at University of Edinburgh)
  • Matilda Toivakka (MSc student, now PhD student at University of Edinburgh)
  • Florian Wollweber (MSc student, now PhD student at Freiburg University, Germany)
  • Jia (Brian) Yunxiang (MSc student, returned to China)
  • Laure Gambardella (Postdoc, currently at University of Cambridge)
  • Tiziana Napolitano (da Vinci placement, now PhD student at Institut Valrose, Nice, France)
  • Elena Morelli (da Vinci placement, now PhD student at European Institute of Oncology, Milan, Italy)
  • Helen Craig (PhD student, now a science teacher in the West Country)
  • Flora Tomasello (research assistant, left to run an imaging facility in Sicily)
  • Susann Voigt (da Vinci placement, currently a PhD student at Kiel University, Germany)
  • Bethany Hughes (research assistant, turned chef)
  • Janina Nahler (BSc Honours project student, now PhD student at University of Oxford)
  • Eleanor Burns (BSc Honours project student, now training to be a science teacher)

Sources of Funding

Medical Research Council

Arthritis Research UK

Biotechnology and Biological Sciences Research Council

GlaxoSmithKline

British Heart Foundation

More information on funding at Sonja Vermeren's Research Explorer profile.