Principal Investigator
MRC Fellow
Lecturer
Trinity College Fellow
Milka Sarris is accepting applications for PhD students.
Research Interests
Cell movement is essential for animal development, wound healing and defence from infection. We are interested in how cell movement is guided to functional destinations. We focus on cells of the immune system (leukocytes), which are remarkably capable of traversing different tissue environments and migrating on demand to sites where their antimicrobial function is needed.
Our aim is to understand how these highly motile cells search tissues and read guidance signals. What are the molecular cues that guide leukocytes to areas of infection or injury? How do these signals propagate and become presented in tissue environments? And how is this information processed by leukocytes? In other words, how do gradients of stimuli instruct cell polarity, cytoskeletal dynamics and migration behaviour?
To address these questions, we exploit the zebrafish larva, whose small size and transparency make it ideal for high-resolution in vivo imaging. We record leukocyte dynamics using advanced microscopy techniques and use quantitative and statistical methods to determine how these are modulated by directional signals. We combine this with a variety of genetic or chemical manipulations, to functionally link molecular, cellular and tissue parameters of leukocyte guidance. Through this integrated approach, our goal is to obtain a better understanding of how leukocytes, and eukaryotic cells in general, interpret complex spatial cues.
Collaborators
Dennis Bray (PDN, University of Cambridge)
Jean-Baptiste Masson (Janelia Farm HHMI)
Philippe Bousso (Institut Pasteur)
Lab members
Caroline Coombs (PhD student)
Alexis Crockett
Hugo Poplimont (PhD student)
Antonios Georgantzoglou (post-doc)
Past members
Edward Mawdsley
Kim Westerich
Teaching
PDN Part II (Cell Assembly and Interactions)
Key Publications
Poplimont H., Georgantzoglou A., Boulch M., Coombs C., Papaleonidopoulou F., Sarris M (2019), Neutrophil swarming in damaged tissue is orchestrated by connexin-dependent calcium signals. bioRxiv, doi: https://doi.org/10.1101/853093
Coombs C, Georgantzoglou A, Walker HA, Patt J, Merten N, Poplimont H, Busch-Nentwich EM, Williams S, Kotsi S, Kostenis E, Sarris M (2019) Chemokine receptor trafficking coordinates neutrophil clustering and dispersal at wounds in zebrafish,
Nature Communications volume 10, Article number: 5166
Sarris M, Olekhnovitch R, Bousso P, (2016), Manipulating leukocyte interactions in vivo through optogenetic chemokine release, Blood
Sarris M, Sixt M, (2015), Navigating in tissue mazes: chemoattractant interpretation in complex environments, Curr. Opin. Cell Biol, 36, 93-102
Sarris M, Masson JB, Maurin D, Van der Aa LM, Boudinot P, Lortat-Jacob H, Herbomel P, (2012), Inflammatory chemokines direct and restrict leukocyte migration within live tissues as glycan-bound gradients, Current Biology, 22, 2375-82
Sarris M, Betz AG, (2011), Live imaging of dendritic cell-Treg cell interactions, Methods in Molecular Biology, 707, 83-101
Sarris M, Betz AG, (2009), Shine a light: imaging the immune system, European Journal of Immunology, 39, 1188-1202
Sarris M, Andersen KG, Randow F, Mayr L, Betz AG, (2008), Neuropilin-1 expression on regulatory T cells enhances their interactions with dendritic cells during antigen recognition, Immunity, 28, 402-413