BEGIN:VCALENDAR VERSION:2.0 PRODID:-//132.216.98.100//NONSGML kigkonsult.se iCalcreator 2.20.4// BEGIN:VEVENT UID:20250804T012250EDT-3349pOMNUI@132.216.98.100 DTSTAMP:20250804T052250Z DESCRIPTION: \n\nOn Friday\, February 24\, 2023\, Nilmar Moretti\, PhD\, As sistant Professor in the Department of Microbiology\, Immunology and Paras itology at the Federal University of Sao Paulo\, Brazil\, will be giving a talk entitled 'Modifying to adapt: the impact of protein acetylation in L eishmania differentiation”. This joint special seminar is cohosted by the ɬ﷬ Research Centre on Complex Traits (MRCCT)\, the Departme nt of Microbiology and Immunology and the Dahdaleh Institute of Genomic Me dicine.\n\n\n Time: 11:00 am\n Date: February 24\, 2023\n Location: McIntyre Building\, Karp Amphitheater - Room 501\n\n\n \n\nAbstract:\n\n“Protein ac etylation has been implicated in the regulation of essential cellular proc esses in diverse prokaryotes and eukaryotes\, including protozoan parasite s. Previous proteomic analysis from our group revealed differential protei n acetylation among the three main Leishmania mexicana stages (procyclic\, metacyclic and amastigote)\, suggesting a central role for this modificat ion during parasite differentiation. Lysine acetylation is regulated by ly sine acetyltransferases (KATs)\, which add acetyl groups to lysines\, and lysine deacetylases (KDACs) that remove the acetyl groups. To better under stand the role of protein acetylation in the Leishmania stage differentiat ion we characterized the four zinc-dependent lysine deacetylases (DAC1\, 3 \, 4 and 5) and found that DAC1 and 3 are essential for the parasite\, whi le DAC4 and 5 are dispensable. Moreover\, DAC1 and 5 are cytosolic and DAC 3 and 4 are nuclear\, suggesting distinct function of these enzymes. Pheno type screening assays using the mutant parasites demonstrated that DAC1\, 3 and 5 are involved in procyclic multiplication\, while DAC1 and 5 gene k nockout impairs differentiation from procyclic to infective metacyclics in vitro. Experimental in vivo infection of Lutzomyia longipalpis further co nfirmed the importance of DAC5 for parasite differentiation by revealing i mpaired metacyclogenesis. In addition\, we found that the absence of DAC5 significantly affects procyclic differentiation to axenic amastigotes and vice versa\, which might be related to morphological alterations observed during time-course differentiation experiments. Finally\, we evaluated the impact of DACs in the progression of host infection in vitro and in vivo. We found a significant reduction in intracellular amastigote multiplicati on of DAC5 null mutants in vitro compared to the parental cell line. A sim ilar scenario was observed in the mouse in vivo infection assays for DAC5 mutants\, with no apparent lesion development compared to parental parasit es. Altogether\, these results suggest that regulation of protein acetylat ion levels is important for Leishmania stage differentiation\, opening the opportunity to explore DACs as potential drug targets and to obtain live attenuated vaccinal strain in a near future”\n DTSTART:20230208T211500Z DTEND:20230208T211500Z LOCATION:Room 501\, McIntyre Medical Building\, CA\, QC\, Montreal\, H3G 1Y 6\, 3655 promenade Sir William Osler SUMMARY:Joint Special Seminar: “Modifying to adapt: the impact of protein a cetylation in Leishmania differentiation URL:/sbms/moretti-seminar-2023-02-24 END:VEVENT END:VCALENDAR