Three Vidi grants for RIMLS researchers 2014

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Three experienced researchers in the Radboud Institute for Molecular Life Sciences have been awarded prestigious NWO-Vidi grants, each 800.000 Euros, to develop their own  innovative lines of research.

Vidi is part of Innovational Research Incentives Scheme from the Netherlands Organisation for Scientific Research (NWO). Vidi is aimed at outstanding researchers who have carried out their doctorates and several years of successful research. NWO selected the winners based on the quality of the researcher, the innovative nature of the research, the expected scientific impact of the research proposal and opportunities for knowledge utilization. 

The RIMLS management congratulates Sander  Leeuwenburgh, Dept. of Biomaterials, Taco Kooij, Dept. of Medical Microbiology and Jelle Goeman, Dept. of Health Science with this Vidi grant and wishes them every success in their projects.

Leeuwenburgh , SanderDr. ir. S.C.G. (Sander) Leeuwenburgh, Radboudumc - Dept. of Biomaterials

Towards load-bearing bioceramics: smart toughening of calcium phosphate cements.

Calcium phosphate cements (CPCs) are widely used to regenerate damaged or diseased bone tissue in dental and orthopedic surgery due to their excellent clinical handling behavior, biocompatibility, unlimited supply and absence of donor site morbidity. Unfortunately, these injectable materials are too brittle for use in load-bearing applications which require toughness, i.e., absorption of energy without unpredictable failure. Since the last decade, CPCs have been mixed with numerous polymers, but the reinforcing effect of these strategies has been disappointingly limited since the polymers did not bind sufficiently to the CPC. Therefore, the goal of the current proposal is to develop tough, load-bearing CPCs by incorporation of innovative, calcium-binding polymeric reinforcements.

Previously, I developed nanocomposites which displayed unique self-healing and mineral-adhesive behavior by combining calcium phosphate nanoparticles with innovative polymers functionalized with calcium-binding bisphosphonate groups. Here, I propose to extend this promising concept by developing calcium-binding polymeric fibers and continuous networks for reinforcement of CPCs. These calcium-binding polymeric reinforcements will form reversible, non-covalent coordination bonds with CPC, thereby allowing for energy dissipation - or even self-healing behavior - similar to highly effective toughening mechanisms based on sacrificial bonds observed in natural materials such as bone.

My team will obtain fundamental understanding of the toughening mechanism by combining micromechanical characterization with computational modeling of the interface between CPCs and bisphosphonated polymeric reinforcements. As a consequence, conventional trial-and-error exercises can be avoided. The proposed work will cause a paradigm shift in our efforts to overcome the brittleness of (bio)ceramic materials. These novel, tough calcium phosphate cements will be made of biocompatible, biodegradable constituents that can be produced using scalable technologies in collaboration with two world-leading industrial partners, thereby creating ideal conditions for clinical translation and commercialization.

Kooij , TacoDr. T.W.A. (Taco) Kooij, Radboudumc - Medical Microbiology

Unravelling the Plasmodium mitochondrion: systematic functional characterization of an essential organelle for anti-malarial drug target identification.

Malaria parasites (genus Plasmodium) belong to an ancient clade of single-cell eukaryotes. They harbour a single mitochondrion that is a suitable target for anti-malarial drug development (e.g. atovaquone). Nevertheless, this organelle and its estimated ~400-500 proteins are poorly understood. Here, I propose to use a systematic approach to unravel the functioning of the malaria parasite mitochondrion and to identify novel targets for the development of anti-malarial drug interventions.

I will start with the identification of the Plasmodium mitochondrial proteome via mass spectrometry of purified mitochondria. Combining these data with various other types of genome-wide data sets in a computational framework will allow the generation of a list of putative and known Plasmodium mitochondrial proteins that approaches completeness. These data will be incorporated in a parasite metabolic model to predict and interpret essentiality of enzymes in Plasmodium blood-stage metabolism. In an experimental genetics exercise of unprecedented scale in malaria research, I will target all genes encoding mitochondrial proteins in the murine malaria model parasite Plasmodium berghei. Essentiality during blood infection will be established in batches of ~100 genes using gene-deletion plasmids that allow identification of successfully mutated parasites by next generation sequencing. Next, I will develop and employ a method enabling the simultaneous generation and isolation of 20 gene-deletion mutants using multiple fluorescent marker combinations. Monitoring of life cycle progression and mitochondrial morphology will shed light on redundancy or stage-specific functions of the deleted genes.

While the generated mutant parasite lines will be made available to the malaria research community, the newly developed method for the generation and isolation of recombinant parasites will pave the way for a genome-wide endeavour. The generated functional data will be used to validate and improve the Plasmodium mitochondrion model, thus enabling a systematic prediction and interpretation of novel anti-malarial drug targets.

 

Goeman, JelleDr. J. J. (Jelle) Goeman (m), Radboudumc - Dept. for Health Evidence

Making uncertainties in rankings visible.

A ranking has always a winner and a loser, but when the real differences are small, coincidence  often plays a major role. The researchers are designing methods to show how confident we are about the found ranking.


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