Starts as a Group Leader January 2025
Our bodies are continuously challenged by external and internal microscopic materials that include microorganisms, ‘bad’ cholesterol, dead cells (over 200 billion cells die within our bodies every day) and protein aggregates. If these materials are not promptly cleared from our system, they can lead to a wide range of diseases that include infections, heart disease, autoimmunity and neurodegeneration.
Specialized cells called phagocytes (which include immune cells such as macrophages and microglia) are tasked with the recognition, clearance and degradation of potentially harmful particulate materials from our tissues and circulation. Our team aims to understand how phagocytes are capable of ‘eating’ and processing very large numbers of widely diverse materials on an ongoing basis while remaining healthy and functional throughout their lifespan, which can range from months to years.
We study this using high-throughput genetic (CRISPR-based) technologies, which allow us to interrogate all the genes in the genome in an unbiased manner. We combine this powerful approach with advanced microscopy, biochemistry and physiology methods to understand how individual gene products (proteins) of interest work in phagocytes during the clearance of particulate materials. This interdisciplinary, multiscale approach allows us to identify and characterise the components that allow phagocytes to function and how they are altered in the abovementioned diseases.
Selected Papers
- Levin-Konigsberg, R., Mitra, K., Nigam, A., Spees, K., Hivare, P., Liu, K., Kundaje, A., Krishnan, Y., Bassik, M.C. (2023)
SLC12A9 is a lysosome-detoxifying ammonium - chloride co-transporter
bioRxiv - Fazeli, G., Levin-Konigsberg, R., Bassik, M.C., Stigloher, C., Wehman, A.M. (2023)
A BORC-dependent molecular pathway for vesiculation of cell corpse phagolysosomes
Curr Biol 33(4): 607-621 - López-Haber, C., Levin-Konigsberg, R., Zhu, Y., Bi-Karchin, J., Balla, T., Grinstein, S., Marks, M.S., Mantegazza, A.R. (2020)
phagosomes for TLR4 signaling and MHC-II presentation in dendritic cells
Proc Natl Acad Sci U S A 117(45): 28251-28262 - Levin-Konigsberg, R., Montaño-Rendón, F., Keren-Kaplan, T., Li, R., Ego, B., Mylvaganam, S., DiCiccio, J.E., Trimble, W.S., Bassik, M.C., Bonifacino, J.S., Fairn, G.D., Grinstein, S. (2019)
Phagolysosome resolution requires contacts with the endoplasmic reticulum and phosphatidylinositol-4-phosphate signalling
Nat Cell Biol 21(10): 1234-1247 - Levin, R., Hammond, G.R.V., Balla, T., Camilli, P.D., Fairn, G.D., Grinstein, S. (2017)
Multiphasic dynamics of phosphatidylinositol 4-phosphate during phagocytosis
Mol Biol Cell 28(1): 128-140 - Levin, R., Grinstein, S., Canton, J. (2016)
The life cycle of phagosomes: formation, maturation, and resolution
Immunol Rev 273(1): 156-79