Geert Van Loo

“Study of the (patho)physiological role of NF‑κB inhibitors A20 and ABINs through genetic modifications in the mouse”

Geert Van Loo was born in 1971 in Belgium. He obtained a Master in Bioengineering in Chemistry in 1994, a Master in Biotechnology in 1996 and a PhD in Biotechnology in 2002, at Ghent University.

The granted project is entitled: “Study of the (patho)physiological role of NF-κB inhibitors A20 and ABINs through genetic modifications in the mouse”. Nuclear factor- κB (NF-κB) is a transcription factor that is a critical regulator of genes involved in innate and adaptive immunity, inflammation, development and suppression of apoptosis. NF-κB-dependent gene expression and apoptosis play crucial roles in numerous cellular processes, and defects in their regulation contribute to a variety of diseases including inflammatory and autoimmune diseases, neurological disorders and cancer. As such, NF-κB signalling needs to be tightly regulated and one of the critical regulators of this process is the cytoplasmic zinc finger protein A20, which has been characterized as a dual inhibitor of both NF-κB activation and apoptosis. Mice deficient for A20 develop severe inflammation and cachexia, are hypersensitive to TNF and LPS, and die shortly after birth, excluding its in vivo study in the adult organism and in diseased pathology. In vivo experiments using conditional gene knockouts and knockins of potentially important mutants are critically important for evaluating the role of a factor in physiological and pathological conditions. The aim of the project is to understand the function, activation and regulation of NF-κB activation by A20 and A20 interacting ABIN proteins, using conditional gene targeting in the mouse. Three particular aims are central in this project: to investigate the physiological role of A20 and ABINs by generating mice with conditional alleles for the gene allowing deletion of the protein by crossing them to cell specific Cre transgenic lines; to study the (patho)physiological role of A20 and ABINs by using the conditional knockout mice in different established inflammatory disease models; and to generate a knocking A20-TAP fusion mutant which would allow us to identify in vivo the binding partners of A20 in different tissues and/or upon stimulation with known activators of the NF-κB pathway and/or in specific disease states.

The jury concludes that Geert Van Loo has undoubtedly the technical and scientific maturity to lead a laboratory. The juy also appreciates that he has well cited publications in a very competitive area. The proposal fits very well in the current research of Geert Van Loo and aims to investigate in vivo the role of negative regulators of NF-κB signalling in physiology and disease pathology. This project will certainly yield very interesting results.