Speaker 1: Prof. Matthew Groves, Associate Professor, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands.
Title of the talk: Allosteric inhibition in aspartate transcarbamylase: Applications from malaria to herbicides
Abstract: Pyrimidine biosynthesis is an essential function in all living cells and is supported by two distinct pathways: de novo synthesis and salvage. Different cell types are more dependent upon different pathways, but generally rapidly dividing cells are dependent on de novo synthesis. Aspartate transcarbamylase catalyses the first committed reaction in this pathway and is therefore an attractive drug target for multiple systems. However, the current ATCase gold standard inhibitor is a transition state mimic and has limited selectivity between human and pathogens. In this talk, I will describe the discovery of a new allosteric inhibitor of ATCase and its potential in multiple disease systems and as a herbicide.
Speaker 2: Hong Yan,
PhD student at the department of Molecular Pharmacology, Groningen Research
Institute of Pharmacy, Groningen, The Netherlands.
Title of the talk: Air pollution
particles accelerate RSL-3-induced ferroptosis in HT22 cells via cAMP-Epac1
Abstract: Air pollution exposure is one
of the important threats to human health. Diesel combustion produces diesel
exhaust particles (DEP) which seem to contribute to the onset of different
neurological diseases due to the induction of oxidative stress, inflammation,
and neuronal degeneration. Underlying molecular mechanisms are ill-defined.
RSL-3-induced neurotoxicity has been linked to the newly identified
iron-dependent form of cell death ferroptosis. Cyclic adenosine monophosphate
(cAMP) seems to be linked to the ferroptosis type of cell death in processes
involving Epac (exchange protein directly activated by cAMP. In this talk, I
will describe a potential interaction between RSL-3-induced neurotoxicity and
DEP, and discuss the role of the cAMP-Epac1 pathway in the combined cell death.