Professor of Immunobiology
I am professor of Immunobiology and head of the Animal Sciences & Health research cluster. I am interested in host-pathogen interactions and work with zebrafish models for infection with intracellular bacterial pathogens, like Mycobacteria and Salmonella, to study mechanisms of host defence.
My research focuses on the immunobiology of host-pathogen interactions. I study mechanisms of host defence against intracellular bacterial pathogens responsible for infectious diseases like tuberculosis and typhoid fever. The causative agents of these diseases, Mycobacteria and Salmonella, parasitize one on the major cell types of the innate immune system, the macrophage. In my group, we use the optically transparent and genetically accessible early life stages of the zebrafish to study macrophage defence mechanisms in a whole organism model system.
Host-pathogen interaction mechanisms
Intracellular bacterial pathogens, such as Mycobacteria and Salmonella, have a remarkable ability to manipulate host signaling pathways in order to promote their survival and spreading through host tissues. In my group we use reverse genetics approaches to study the host factors involved in combatting these persistent pathogens. We also study responses to opportunistic pathogens, like Staphylococcus bacteria and Aspergillus fungi. Recent work has shed new light on the interaction between macrophages and neutrophils in nitric oxide mediated host defence. Furthermore, current research efforts are strongly concentrated on the discovery of an autophagy regulator that protects against mycobacterial infection and that forms a missing link between pathogen recognition and autophagic host defence. In collaborative projects we also use our infection models to screen for novel immunomodulatory drugs for infectious disease treatment.
Activation of the immune defences
We developed zebrafish models for immunodeficiency and autoinflammation by mutation or knockdown of central factors in innate immunity signaling, conserved between the zebrafish and human. By RNA sequencing of whole infected embryos and sorted macrophages, we gained insight into the host immune response genes activated at specific stages of infection with different pathogens. Based on these extensive expression profiling studies, we selected host genes for loss and gain of function studies. Genes currently under investigation include several early macrophage-specific genes, such as a receptor that we have shown to be required for macrophage migration to chemokine signals released at infection foci and that contributes to the dissemination of mycobacterial infection through host tissues. The ultimate aim of these studies is to identify host targets for development of novel therapeutic strategies.
Current group members
- Monica Varela Álvarez – postdoc, Marie Curie IEF
- Tomacz Prajsnar – postdoc, Marie Curie IEF
- Bjorn Koch – postdoc, EU
- Michiel van der Vaart – postdoc, STW
- Samrah Masud – PhD student, HEC Pakistan fellowship
- Rui Zhang – PhD student, CSC fellowship
- Ralf Boland – PhD student, STW
- Yufei Xie – PhD student, CSC fellowship
- Frida Sommer – CONACYT fellowship
- Karin Bosma - Fish facility coordinator
Previous group members
- Vincenzo Torraca – PhD student, FishForPharma Project
- Julien Rougeot – postdoc, FishForPharma Project
- Erica Benard - PhD student, SmartMix project
- Michiel van der Vaart - PhD student, SmartMix project
- Philip Elks - postdoc, ERS fellowship
- Chao Cui - PhD student, SmartMix project
- Zakia Kanwal, PhD student, HEC Pakistan fellowship
- Peter Racz - postdoc, Marie-Curie fellowship
- Joost van Soest – PhD student, University funding
- Oliver Stockhammer – PhD student/postdoc, University funding/ZF-HEALTH project
- Anna Zakrzewska - postdoc, EU ZF-TOOLS and Horizon Breakthrough project
- Anita Ordas - project manager, FishForPharma project