Biosketch

Dr. Frans Bianchi

Frans obtained his PhD in biochemistry 2016 (GBB, University of Groningen). During his PhD, he studied the mobility, oligomerization and localization of plasma membrane-incorporated amino acid transporters in budding yeast. For his postdoc he transitioned in 2017 into the field of mammalian cell biology, first at the Department of Renal Physiology and subsequently at the Department of Tumor Immunology (both Radboud University Medical Center). Here, he discovered that epitopes derived from membrane proteins were overrepresented on MHC-I complexes and this founded the start of his current research studying membrane protein antigen presentation. Supported by EMBO and FEBS Short-Term Fellowships, he developed novel chemical probes as a postdoc at the Department of Organic Chemistry, Georg-August University (Göttingen, Germany) that enable to study membrane protein antigen presentation at single-molecule and single-cell level. In 2018, Frans obtained a VENI grant and he moved back initially as a postdoc to continue his research in the Molecular Immunology group of GBB, where he now continues his research as a tenure-track assistant professor. Frans his main research interests lie in:

• the role that membrane proteins and lipids play in T-cell activation. Herein he focuses on the intracellular trafficking and immune presentation of antigenic membrane proteins from bacteria and the impact of their membrane composition on this process.

• 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.

Three top publications 2017-2022

1. Bilderbeek R, Baranov M, van den Bogaart G & Bianchi F (2022) Transmembrane helices are an overlooked and evolutionarily conserved source of major histocompatibility complex class II epitopes. Frontiers in Immunology 12: 763044; DOI: https://doi.org/10.3389/fimmu.2021.763044

We used bioinformatics to show that membrane proteins are not only over-presented in MHC class I (as shown in publication #2), but also in MHC class II to helper T cells. Moreover, we found a likely explanation for this: Transmembrane helices are more conserved than soluble protein domains, which likely limits escape mutations where pathogens evade T cell responses.

2. Baranov MV, Bianchi F, ……., Diederichsen U & van den Bogaart G (2019) The phosphoinositide kinase PIKfyve promotes cathepsin-S-mediated major histocompatibility complex class II antigen presentation. iScience 11: 160-177; DOI: https://doi.org/10.1016/j.isci.2018.12.015

In this study, we discovered that the processing of ingested pathogens for presentation to T cells depends on phosphoinositide kinase PIKfyve. I developed the antigen presentation assay which was essential for this study. This paper received much attention (e.g., Derk Lowe’s Blog in Science), because Apilimod was subsequently identified in a large drug screen as the most effective compound for inhibition of SARS-COV-2 infection of human cells. Apilimod is currently being tested in clinical trials for treatment of COVID-19.

3. Bianchi F, Textor J & van den Bogaart G (2017) Transmembrane helices are an overlooked source of Major Histocompatibility Complex class I epitopes. Frontiers in Immunology 8: 1118; DOI: https://doi.org/10.3389/fimmu.2017.01118

Using bioinformatics, we correlated transmembrane helices with MHC-I epitopes in the human proteome. This revealed that peptides derived from transmembrane helices are more likely to be presented to cytolytic T cells. Moreover, we found that many clinically important and immunodominant MHC epitopes stem form transmembrane helices. I designed this study and performed most of the work.

For further reading: group website and RUG Profile page