Faculty of Science will participate in the NCOH programme

One of the projects, led by Hans de Cock and Seino Jongkees, focuses on the development of new antifungals. Aspergillosis is a lung associated Aspergillus fumigatus infection, which can lead to chronic infection in people with cystic fribrosis, resulting in decreased respiratory function. The resistance of Aspergillus fumigatus strains to antifungal agents is increasing and above all there are few antifungal agents available. In dogs it has already been demonstrated that the fungus adapts in dogs by accumulating mutations and there are also indications that such adaptations occur in human patients. "To effectively treat patients in the future we need to understand the adaptation of Af in airways of CF patients and to develop new antifungals.”

Much One Health research depends on the accurate and sensitive detection of microbes and viruses in environmental sequencing datasets (metagenomes). Identifying viral sequences in metagenomes is like searching for a needle-in-a-haystack because their sequences cannot be recognized with commonly used homology-based search tools. In this PhD-project, led by Bas E. Dutilh, Ronnie de Jonge and Marion Koopmans, researchers will integrate innovative machine learning and statistical approaches into a sensitive virus detection tool. “We will apply the tool to important plant-, human-, and other NCOH datasets. Our novel computational tools for virus identification in a range of biomes – including healthy and diseased humans, farm animals and wildlife – will lead to a better understanding of the role viruses in human, plant, animal, and environmental systems.”

The present rate of generation and approval of human vaccines or therapeutic antibodies is too low to control newly emerging virus diseases as seen during the recent Ebola virus outbreaks. To increase our pandemic preparedness, there is an urgent need for preventive antiviral strategies with broad-range efficacy to control future emerging zoonotic viruses. In this PhD-project, led by Sabrina Oliveira, Xander de Haan en Paul van Bergen en Henegouwen, complements the existing consortium strategy by including complementary expertise on single domain antibody (nanobody) technology. “In this project, novel nanobodies binding to conserved epitopes on viral proteins from corona- and influenza viruses will be generated. After thorough characterization of their binding properties, these nanobodies will subsequently be explored for application in diagnosis, protection, and treatment of viral infection of both men and animals.”

The dramatic rise of multi-drug resistant bacteria urgently calls for the development of novel antibiotics that target unexploited pathways. This PhD-project, led by Markus Weingarth, Eefjan Breukink and Tom Wennekes, focusses on a fungal peptide called plectasin. Plectasin shows high activity against drug resistant bacteria and maintains its activity in rodent models. Yet, the available data, fail to explain why the infamous MRSA is resistant to plectasin, while some plectasin analogues show high activity. Using cutting-edge solid-state NMR methods in native lipid membranes and other biophysical methods, we have recently acquired a large and compelling set of data. “Based on our novel insights and methodological edge, we propose two interrelated programs that aim to gain a fundamental structural understanding of MRSA resistance to plectasin and to use this knowledge to break MRSA resistance and design even more powerful plectasin analogues."