Laureates Postdoc stipends 2017
For the call AI&II Postdoc Stipends 2017 we received 25 applications and 12 researchers were invited for the interview round on 23 May. These three researchers have been selected and awarded one of the AI&II Postdoc 2017 stipends:
- Michaela Wenzel, department of Bacterial Cell Biology, Swammerdam Institute for Life Sciences, UvA
Title research proposal: Aiming at the interface – Challenging the Bacterial Cell Envelope with Antibiotics
- Tom Groot Kormelink, department of Experimental Immunology AMC
Title research proposal: Bridging innate and adaptive immunity: mast cells shape dendritic cell-driven immune responses
- Suzanne Bal, department of Experimental Immunology AMC
Title research proposal: The role of ILCs in corticosteroid (in)sensitivity
Suzanne Bal and Tom Groot Kormelink
Suzanne Bal (Spits group) and Tom Groot Kormelink (De Jong group), two researchers from EXIM received the AI&II Postdoc stipend in the inflammatory disease program. The project of Suzanne Bal will aim at the role of ILC2s in neutrophilic asthma. Tom Groot Kormelink will investigate the role of mast cells in DC maturation and DC-driven activation and polarization of naive T cells in humans.
In recent years innate lymphoid cells (ILCs) have emerged as important players in inflammatory diseases such as asthma. Suzanne Bal will investigate the role of ILC2s in neutrophilic asthma. Standard treatment of asthma involves application of glucocorticoids. A proportion of patients are resistant to the immune suppressive effects of glucocorticoids, including those with neutrophilic asthma. As we have shown that ILC2s are highly plastic cells that can change from an IL-5 producing cell into an IL-17 producing cell, we hypothesize that ILC2s from patients with neutrophilic asthma display more of an IL-17 profile, a feature that is indicative of glucocorticoid resistance. By analysis of the transcriptome and epigenome of IL-5 and IL-17 producing ILC2s we will obtain insight into how these cells change when they become IL-17 producers and elucidate mechanisms involved in corticosteroid insensitivity. Better understanding of these mechanisms should lead to the identification of novel targets for therapeutic intervention. It is increasingly recognized that innate immune cells potentiate and/or modulate dendritic cell (DC)-driven adaptive immune responses.
Tom Groot Kormelink will investigate the role of mast cells in DC maturation and DC-driven activation and polarization of naive T cells in humans. Different immunomodulatory mechanisms will be investigated, including the role of extracellular vesicles in mast cell-DC communication. Since mast cells and DCs localize in close proximity in peripheral and lymphoid tissues, and mast cells are associated with both pro- and anti-inflammatory functions, knowledge on the DC modulating capacities of mast cells may reveal their role in aberrant immune responses observed in inflammatory diseases, and could lead to novel therapeutic options. In addition, the knowledge on the mechanisms by which mast cells either enhance or inhibit specific T cell responses can be used for developing new vaccine strategies.
Michaela Wenzel (Leendert Hamoen group at the UvA) received the AI&II Postdoc stipend in the infectious disease program. Her project title is: Aiming at the interface – Challenging the Bacterial Cell Envelope with Antibiotics.
Michaela obtained her PhD from the Ruhr University Bochum in Germany on the bacterial response to membrane-active peptide antibiotics. For her postdoc period she move to Amsterdam, working on the effect of antibiotics on bacterial membrane proteins. Her main interest is understanding the mode of action of antibiotics that target the bacterial cell envelope. For this she is mainly using biochemical and fluorescence microscopy techniques, including super resolution microscopy.
Antibiotics that target the bacterial cell envelope, especially the cytoplasmic membrane, hold great potential to be resistance-breaking and due to their complex targets promise slower resistance development than antibiotics with single proteinaceous targets. Importantly, membrane-active compounds have the ability to kill non-growing cells, which is of key importance for treating chronic and recurrent bacterial infections. The killing mechanism of an antibiotic is of key importance for its clinical success since it determines how effectively bacteria are killed and how fast resistance occurs. Therefore, new drug development strongly profits from understanding how successful antibiotics kill bacteria. However, only very few cell envelope-targeting antibiotics are characterized in sufficient mechanistic detail and even less are comprehensively characterized in vivo.
Recently, Michaela could show that the last line of defense antibiotic daptomycin does not act by disrupting membrane integrity, which was believed for the last 30 years based on in vitro studies. In living bacteria however, it preferentially inserts into specialized membrane microdomains that harbor the lateral cell wall synthesis machinery and disturbs proteins involved in cell wall and membrane synthesis, perfectly underscoring how little we know about how even established antibiotics kill bacteria.
Michaela is currently working with the non-pathogenic model organism Bacillus subtilis in the lab of Leendert Hamoen at the UvA, but, in view of the growing threat imposed by drug-resistant tuberculosis infections, she would like to expand her expertise towards mycobacteria and will join the laboratory of Wilbert Bitter (Medical Microbiology) in the O2 building.