Jurgen Haanstra ’s project, which is together with Ruud Brakenhoff from Amsterdam UMC-Cancer Center Amsterdam (A-UMC-CCA), will focus on metabolism in head-and neck cancer. Head and neck cancer arises in the mucosal linings of the upper-aerodigestive tract and is generally preceded by precancerous changes that may be visible as lesions. In total 50% of patients die of the disease despite invasive treatments. We recently discovered that these tumors rewire their metabolic program atypically. In this project they will use computer models and laboratory experiments to study this atypical metabolic program. They will investigate why these tumor cell reprogram metabolism in this remarkable way, and how this can be exploited to improve diagnosis and treatment of these tumors and their preceding precancerous mucosal changes.
The project of Rob Leurs and Henry Vischer deals with the rare genetic brain disease Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC), wherein mechanisms to regulate brain volume are disrupted. Children affected with MLC face a life of increasing motor and cognitive handicap. Drug treatment is currently unavailable. A recent insight from the clinic forms the basis of the project: child neurologist Marjo van der Knaap and neuroscientist Rogier Min from AUMC discovered defects in a newfound protein in a small group of MLC patients. But not much is known about this protein, a so-called G-protein-coupled receptor (GPCR). GPCRs enable cells to respond to external stimuli, and are exceptionally suited as drug targets. Therefore, this GPCR might be an urgently needed therapeutic target for MLC. In this project, the team of Leurs – specialized in the investigations of GPCRs – will investigate how the receptor signals, and search for drug-like modulators. Dr. Min and his team of neuroscientists will investigate how the GPCR is involved in brain volume regulation. Finally, the teams will test whether GPCR modulation can be used to treat MLC in preclinical models.
Martine Smit’s project together with Michiel Pegtel from the A-UMC-CCA aims to unravel how virus-encoded receptor proteins exploit the extracellular vesicle (EV) machinery and contribute to cell survival and immune evasion. A growing body of evidence indicates that viruses are causatively involved in approximately 15% of all malignancies. Human Cytomegalovirus (HCMV) encodes G protein-coupled receptors (GPCRs) that modulate signaling networks implicated in cancer hallmarks. We discovered that these viral GPCRs are selectively enriched in and actively secreted through EVs. Since EVs are known to contribute to cancer progression, these studies might disclose novel pathways by which these viral GPCRs drive cancer progression and immune evasion. In this project we will combine the expertise of viral GPCR signaling/nanobodies (Smit/Siderius/Heukers), EV biology (Pegtel/Crudden) and herpesviruses (Pegtel/Smit) using newly developed EV sensors and state-of-the-art imaging, genetic screens, biochemical tools and a unique set of viral GPCR-directed nanobodies.
ZonMW Open Competition
ZonMw Open Competition funds research proposals for non-programmed, fundamental research. This funding instrument has no thematic limitations and focuses on research proposals in all scientific disciplines with a question or problem that concerns, or overlaps with, fundamental research into healthcare and innovation.
Through this programme, ZonMw wants to bring together researchers from two or more disciplines to facilitate excellent team science that results in innovative (groundbreaking) research of exceptional quality in the field of healthcare research. The expected outcome of a project is primarily scientific advancement (increased knowledge, development of modelling and theory) within a new collaboration between research groups (team science). ZonMw considers this open stimulus for science to be the primary driver for innovation in science and healthcare for the longer term.