Bianchi group
Frans Bianchi (Assistant Professor)
F.Bianchi at rug.nl
ORCID: 0000-0002-9385-9695
ResearcherID: E-8796-2018
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Research
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Watch Frans Bianchi explain his research. Movie from eye-openers.nl.
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I am a trained biochemist working in cell biology and especially immunology. My fascination in science is the communication between cells that leads to a selective immune response against pathogenic bacteria, but at the same time enables to tolerate the vast majority of commensal bacteria that live in our intestine and on our skin. I now employ my experience as a biochemist in membrane biology to develop tools to investigate this communication. My main research interest is the role that membrane proteins and lipids play in T cell activation. Herein I focus on the intracellular trafficking and immune presentation of antigenic membrane proteins from bacteria and the impact of their membrane composition on this process.
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In a bioinformatics study, I showed together with my co-workers that epitopes presented in MHC class I and II are several-fold enriched for peptides derived from transmembrane helices (depending on the haplotype). This founded the basis of my groups current research aimed at elucidating the molecular mechanisms of antigen presentation/cross-presentation of transmembrane helix-derived epitopes.
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A second research focus is the development of novel tools to investigate the relationship between bacterial infections and breaking of B-cell tolerance. The working model for this research is that the formation of hybrid-autoantigens, a complex of a microbial and a human protein, leads to an unwanted activation of self-reactive B-cells. An example of this is the disease anti-neutrophil cytoplasmic antibody-associated (ANCA) vasculitis where autoantibodies against neutrophils and monocytes cause chronic inflammation in the small blood vessels. In ANCA-vasculitis, the loss of self-tolerance is likely an unwanted consequence of the immune response against neutrophil antagonists produced by the opportunistic pathogen Staphylococcus aureus (project funded by a ZonMw Off-Road grant and in collaboration with UMCG, 2020).
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I obtained my PhD in biochemistry (2016, Department of Membrane Enzymology, University of Groningen, the Netherlands). During my PhD, I studied the mobility, oligomerization and localization of plasma membrane-incorporated amino acid transporters in budding yeast using advanced microscopy and spectroscopy techniques (single particle tracking, super-resolution microscopy, circular dichroism). I showed that the localization of these plasma membrane proteins in Saccharomyces cerevisiae is mainly dependent on protein conformation in combination with an anomalously slow diffusion. Furthermore, I identified that steric interactions of large cytosolic domains form the predominant barrier of this impaired lateral diffusion. I also identified and characterized a novel sequence for lipid-anchoring by fluorescence spectroscopy techniques. Finally, I compared transport fluxes of eukaryotic and prokaryotic basic amino acid transporters using reconstituted proteins in proteo-liposomes with radioactively labeled substrate.
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For my post-doctoral training, I worked at the Department of Physiology (Radboud University Medical Center) in 2016. Here, I analyzed the dimerization of splice forms of the thiazide-sensitive NaCl cotransporter using Förster resonance energy transfer with fluorescence lifetime imaging microscopy.
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I did a second post-doctoral training at the Department of Tumor Immunology (Radboud University Medical Center) in 2017. Here I found that epitopes derived from membrane proteins were overrepresented on MHC-I complexes, this founded the start of my current research studying membrane protein antigen presentation for, which I received a VENI grant from the Dutch Organisation for Scientific Research in 2018 to setup systems that allow to study membrane protein antigen presentation. I also received an EMBO and href="http://www.febs.org/"target="_blank">FEBS Fellowship (2017) to develop novel chemical probes as a postdoctoral fellow at the Department of Organic Chemistry, Georg-August University, Göttingen, Germany.
PhD thesis:
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Kinetics, dynamics and localization of basic amino acid transporters in Saccharomyces cerevisiae.
Link to thesis
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Awards and Fellowships:
- 2020: Off Road grant from ZonMW
- 2018: VENI grant from the Netherlands Organisation for Scientific Research (NWO)
- 2017: European Molecular Biology Organization (EMBO) Short-term Fellowship
- 2017: Federation of European Biochemical Societies (FEBS) Short-term Fellowship
- 2017: Erasmus+ staff mobility grant
- 2013: 1st Poster Presentation award, 2013 Annual BE-Basic Symposium, The Netherlands
- 2010: University Fund Groningen for International internship
- 2010: Erasmus Scholarship for International internship