PhD Student in Immunology

University of Bern
January 03, 2023
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PhD Student in Immunology

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Start date: Available immediately. Workplace: Department of BioMedical Research, Visceral Surgery and Medicine, Visceral Surgery Research Labs, University of Bern, Switzerland. Project title: Prevent scar-tissue mediated occlusion of intraperitoneal devices

Background and Motivation

Over the last decade, tissue sensors and automated drug delivery systems have been vastly improved and big steps have been taken to develop closed loop control systems that are closer to fully automated artificial organs. The current generation of closed loop control systems mostly relies on peripheral sensing and drug application. This causes a significant delay which makes these systems difficult to tune. More central sensing and drug application would be preferrable, and the peritoneal cavity would be an ideal place to surgically implant such devices. However, the current generation of intraperitoneally implantable devices is limited because intraperitoneal tubing is rapidly occluded due to excessive intraperitoneal scar formation. Our lab is focus on intraabdominal scar formation and wound healing in the context of post-surgical healing after operations in the abdominal cavity. In fact, we recently uncovered a completely novel mechanism of injury repair that is specific for serous body cavities. We published this story in Science as cover story (1). Here we ask whether the identified mechanisms might be further explored to improve the lifetime of medical devices that are implanted into the abdominal cavity.

Research Work

The overarching hypothesis to be tested is that implanted peritoneal devices lose their patency due to immune-mediated excessive scarring. We hypothesize that this process is induced by the foreign material of the device, the injected pharmaceuticals, or a combination thereof. We aim to: • Decipher the peritoneal immune response to foreign material, large-molecule pharmaceuticals, and a combination thereof. • Establish a surgical in vivo open and closed loop system to model loss of patency • Improve peritoneal patency by reverting excessive scar formation

We will use established in vivo systems using cutting edge intravital microscopy of the abdominal cavity, to characterize how the immune system of the peritoneal cavity reacts to injected foreign material, large-molecules, protein-based pharmaceuticals, and a combination thereof. We will use human peritoneal immune cells directly from the operation rooms to investigate the human correlate in vitro (Aim 1). In parallel, we will develop a surgical in vivo system that allows us to model the loss of peritoneal patency in the mouse. We will characterize the scar tissue that occludes peritoneal catheters in the mouse system and correlate it with findings from catheters explanted in humans in our surgical department (Aim 2). Then, we will try to revert the process that leads to excessive scarring with previously investigated approaches that were effective against post-surgical scars. A broad screening (spatial transcriptomics or scRNA-Seq) will reveal a list of additional candidate pathways (Aim 3).

Relevance Uncovering new strategies to keep devices in the peritoneal cavity open, will have significant relevance for several the development of biomedical devices.

The PIs Joel Zindel is a clinician-scientist working 50% in the lab and 50% as a surgeon in the hospital. He has been trained in IVM in the lab of Paul Kubes (University of Calgary). He is passionate about patients, macrophages and microscopes and his mission is to heal peritoneal adhesions.

Daniel Candinas chairs the Department for Visceral Surgery and Medicine. He is passionate about enterpreneurship, has successfully launched several start-up companies, and is very well connected with MedTech industrial partners. In mentoring you, we hope to unlock your potential as inventor.

Requirements

Imagination, the will to invent, and entrepreneurship. Experience with in vivo (mouse or rat) experimental models and a background in microscopy or bioinformatics (R or Python, Java) are of advantage. Good communications skills in English and a master's degree in medicine or life sciences is required.

Salary Employment by the University of Bern. Salary according to Swiss National Science Foundation.

Intellectual property We closely work together with potential commercial partners and protection of intellectual property (patent filing) may delay-but not prohibit-the scientific publication of the results.

What can the student expect?

We offer an opportunity to advance a technological barrier that is limiting several exciting new biomedical therapies. While academically funded and conducted, the project is closely linked to interested industrial partners. It offers training in immunology, IVM, and translational research. You will learn to use state of the art image analysis techniques (Imaris, ImageJ). We offer support by our group-intern bioinformaticians; they are great teachers and will help you develop your bioinformatic skills (R). You will be enrolled in the graduate school for biomedical sciences at the University of Bern and become part of a great group of researchers in a fun and sociable environment. We like to get together and our lab is situated in an extremely lovely, small city in the heart of Europe.

Please apply by sending your application to joel.zindel@dbmr.unibe.ch.

References 1. Zindel J, Peiseler M, Kubes P. Primordial GATA6 macrophages function as extravascular platelets in sterile injury. Science (New York, NY). 2020;In Press 2021.

www. unibe.ch

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