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BPRC

Biomedical Primate Research Centre
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27 Projects, page 1 of 6
  • Funder: European Commission Project Code: 101078667
    Overall Budget: 1,500,000 EURFunder Contribution: 1,500,000 EUR

    What we see depends on what we have in mind. For example, we can quickly find tomatoes in the vegetable department of a supermarket by searching for red and round objects, making them stand out from the background. This is thought to be supported by top-down processing within the hierarchy of areas in the visual cortex, but the detailed neural mechanisms are still poorly understood, partly because of limitations in neural recording technologies. In my lab, we recently developed a three-photon microscope capable of visualizing the activity of large populations of individually-defined neurons in awake and behaving macaque monkeys. Combining this novel imaging modality with well-controlled behavioral tasks provides the exciting opportunity to investigate the neural mechanisms of generative vision at an unprecedented scale and level of detail. We will train macaque monkeys to search for shapes hidden in noisy texture elements, investigate the strategy used by the prefrontal cortex to encode the mental template to guide this search, and how this process warps the encoding of visual information in nearly complete local populations of neurons in early visual areas. We will investigate the topographic organization of the recorded population of neurons, and develop viral and histological tools to determine their cell types as well as their connectivity profiles. We will also use psychophysics to make a link to conscious perception in humans, investigating how a search template can warp perception. Finally, we will incorporate our empirical findings into artificial neural network models with interpretable circuit mechanisms. This is expected to bring the flexibility and robustness of generative vision into models of artificial intelligence, as well as provide a computational framework to define novel hypotheses about the detailed neural mechanisms of generative vision in primates, which we can subsequently test with both behavioral measures and in-vivo recordings.

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  • Funder: European Commission Project Code: 223226
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  • Funder: European Commission Project Code: 101118536
    Overall Budget: 12,572,500 EURFunder Contribution: 11,429,700 EUR

    What? Hypnozoites are dormant liver stage malaria parasites that can reactivate and cause repeated blood-stage infections without the bite of an infectious mosquito. We will, for the first time: - characterize the cellular environment contributing to dormancy at systems level (WP1) - explore the reactivation kinetic and tissue environment of hypnozoites within the natural host (WP2) - functionally characterize host & parasite factors governing dormancy or reactivation (WP3) Why? - Dormancy and reactivation of hypnozoites is an unresolved biological mystery since decades - Dormant parasites are a major obstacle to the curative treatment of malaria The challenge: Tracking the in vivo development and understanding the biology of these rare, quiescent parasites that normally reside inside the liver of the host The solution: A synergistic, multidisciplinary investigation, which is only possible if we combine the unique resources and complementary expertise of three leading laboratories in: - Radiopharmaceutical chemistry for the development of dedicated Positron Emission Tomography tracers for non-invasive investigation of the parasites in situ, as well as to capture infected tissue samples for systems level investigations - Systems biology for simultaneous multi-omics profiling of the parasite and the host cell at single-cell resolution and in the spatial context to be validated by parasitological assays - Parasitology for functional investigation through genetic engineering and manipulation of the parasites in vitro and validation within the natural host Anticipated project outcomes: - Detailed insights into the relapse characteristics of the parasite in vivo - Understanding how host and parasite factors collectively determine the fate of infection - Novel imaging, transfection and omics methods for malaria research and beyond - Opportunities for novel therapeutic strategies for awakening and killing these vicious pathogens

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  • Funder: European Commission Project Code: 733176
    Overall Budget: 4,113,380 EURFunder Contribution: 4,113,380 EUR

    Rabies is the deadliest disease on earth (99.9% fatality rate). Annually, ~58.000 people die from rabies, more than half of them are children. Many remain unvaccinated because of the high costs and the need for a cold-chain. Likewise, despite the existence of an excellent yellow fever (YF) vaccine, yearly ~30.000 people die of YF. The 80-year old low-tech production process does not allow to produce sufficient doses. There is now a real danger that major YF-outbreaks become uncontrollable. We aim at developing an efficient, safe, cheap, thermostable and easy-to-produce vaccine that can be needle-free administered, that protects against both rabies and YF, and that can be implemented in routine prophylactic paediatric vaccination. For this, we will employ our (P01a) proprietary infectious DNA (iDNA) vaccine technology. Simple, even needle-free injection of a low dose (1-10µg) of this easy-to-produce naked plasmid in mice and hamsters launches the YF vaccine virus and protects hamsters as efficiently as the commercial vaccine against lethal YF challenge. The iDNA YF vaccine will be used as vector to express relevant protective rabies antigens. Dual protection of such chimeric iDNA rabies/YF vaccine will be demonstrated against lethal rabies and YFV challenge in small animal models. Likewise, chimeric rabies/Japanese encephalitis and rabies/Zika virus iDNA vaccine candidates will be generated using this versatile platform. Next, induction of protective immunity will be demonstrated in rhesus macaques. The iDNA vaccines combine the benefits of both the YF live-attenuated vaccine (highly efficient life-long induction of immunity) and the thermo-stability, ease-of-production and the potential to customize (in response to emerging medical needs) of “classical” DNA vaccines. A path towards advanced pre-clinical and clinical development of such novel vaccines will be developed in compliance with European regulatory and WHO prequalification requirements.

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  • Funder: European Commission Project Code: 606084
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