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Milka Sarris

We are interested in how cells navigate in complex tissue environments. We focus on immune cells and ask how they search tissues and find their way to sites of infection or tissue damage. We approach this through state of the art live imaging of immune cells in zebrafish combined with quantitative, genetic and optogenetic approaches.
Milka Sarris

Principal Investigator

MRC Fellow

Lecturer

Trinity College Fellow

Milka Sarris is accepting applications for PhD students.


Office Phone: +44 (0) 1223 333542

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 leukocyte motion is organised at sites of tissue damage to generate inflammatory responses. Neutrophils are the first cells to be recruited to damaged loci where they execute important antimicrobial functions, such as phagocytosis or secretion of microbicidal compounds. However, excess neutrophil accumulation and inflammation can cause collateral tissue damage and be detrimental for tissue integrity. How do these cells organise their recruitment to achieve the right magnitude of an inflammatory response? What are the chemical and physical cues that allow them to distinguish damaged from healthy tissue? How do they interpret and integrate these signals? How do they make key decisions such as which way to go, how long to stop and whether to call for reinforcements? If we can understand the logic of neutrophil migratory decisions in their complex native environments, we would be better placed to predict and manipulate the behaviour of these cells in therapeutic settings.

To address these questions in mechanistic detail in vivo, 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 chemical and physical signals. We combine this with a variety of genetic, optogenetic 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 interpret complex environmental cues to generate effective immune responses.

Collaborators

Kristian Franze (PDN, Max Planck Nuremberg)
Ewa Paluch (PDN, University of Cambridge)
Daniel Irimia (Harvard University)
Martin Welch (Biochemistry, University of Cambridge)

Lab members

Hazel Walker
Hugo Poplimont  (PhD student)
Antonios Georgantzoglou (post-doc)

Past members

Kim Westerich
Caroline Coombs (PhD student)
Alexis Crockett
Morgane Boulch

Teaching

Part IB NST Physiology

Part IA MVST Homeostasis

 

Key Publications

Poplimont H., Georgantzoglou A., Boulch M., Coombs C., Papaleonidopoulou F., Sarris M*. Neutrophil Swarming in Damaged Tissue Is Orchestrated by Connexins and Cooperative Calcium Alarm Signals. Current Biology. S0960982220306692 (2020) doi:10.1016/j.cub.2020.05.030. See also preview by Palomino-Segura, M. & Hidalgo, A. Immunity: Neutrophil Quorum at the Wound. Current Biology CB 30, R828–R830 (2020)

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 releaseBlood

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

Plain English

Our bodies are constantly threatened by tissue damage, whether via physical injury or toxic chemicals. Cells of the immune system are remarkably capable of sensing perturbations in our body’s integrity and mobilising themselves towards such compromised loci, in a process referred to as ‘inflammation’. All of us experience the bothersome symptoms of inflammation, namely redness, swelling and pain, at one point or another. These are associated with the infiltration of immune cells, crucial for defending damaged tissue from harmful microbial pathogens. Despite the vital role of inflammation in protecting our body, sometimes this process goes awry, leading to complications and diseases, whereby relevant therapeutics are still limited. We are interested in unravelling mechanisms that allow immune cells to distinguish healthy from damaged tissue and to organise their migratory response to such sites. To study this process at the single cell level in a live organism, we employ powerful microscopy techniques and genetic experimentations in a small model organism, the zebrafish. Through this approach, we are able to visualise and manipulate unforeseen immune cell behaviours within the real setting of tissue damage and infection.

IMG_20170928_170430.jpg

Top row (left to right): Milka, Caroline, Kim
Bottom row (left to right): Antonis, Edward, Hugo

Above: In this video we capture neutrophil swarming at a site of acute wounding as the locus is invaded by opportunistic bacteria.

 

Above: GFP-marked leukocytes (green) recruited to a site of injury. The wound was made by dissecting the tail fin of the zebrafish larva (bottom right).

Above: GFP-marked leukocytes recruited to a local laser wound. The entire anatomy of the zebrafish larva is highlighted by red cell labelling.