WEHI Special Infection and Global Health Seminar hosted by Professor Aaron Jex

Dr Marco Lalle

Istituto Superiore di Sanità, Department of Infectious Diseases; Unit of Foodborne and Neglected Parasitic Diseases,

European Union Reference Laboratory for Parasites, Italy

Giardia 14-3-3 protein: a journey from biological function to drug targeting
Giardia duodenalis is a cosmopolitan zoonotic protozoan parasite causing giardiasis, one of the most common diarrhoeal diseases in human and animals. Beyond its public health relevance, Giardia represents a valuable and fascinating model microorganism. The deep-branching phylogenetic position of Giardia, its simple life cycle and its minimalistic genomic and cellular organization provide a unique opportunity to define basal and "ancestral" eukaryotic functions. The eukaryotic 14-3-3 protein family represents a distinct example of phosphoserine/phosphothreonine-binding proteins. The extended network of protein-protein interactions established by 14-3-3 proteins place them at the crossroad of multiple signalling pathways that regulate physiological and pathological cellular processes. Despite the remarkable insight on 14-3-3 protein in different organisms, from yeast to humans, so far little attention was given to the study of this protein in protozoan parasites. However, in the last years, research efforts have provided evidences on unique properties of the single 14-3-3 protein of Giardia and on its association in key aspects of Giardia life cycle. During this presentation I will summarize the work done in my lab during the last  15 years on the biochemistry and biology of the Giardia 14-3-3 protein and on the possibility to use this protein as target to propose new strategies for developing innovative antigiardial therapy.

Professor Jessica Kissinger

Center for Tropical and Emerging Global Diseases at the University of Georgia, USA

Gene Regulation and Transcription in Cryptosporidium parvum
Once considered rare in eukaryotes, polycistronic mRNA expression has been identified in kinetoplastids and, more recently, green algae, red algae, and certain fungi. This study provides comprehensive evidence supporting the existence of polycistronic mRNA expression in the apicomplexan parasite Cryptosporidium parvum. Leveraging long-read RNA-seq data from different parasite strains and using multiple long-read technologies, we demonstrate the existence of defined polycistronic transcripts containing 2-4 protein encoding genes, several validated with RT-PCR. Some polycistrons exhibit differential expression profiles, usually involving the generation of internal monocistronic transcripts at different times during development. ATAC-seq in sporozoites reveals that polycistronic transcripts usually have a single open chromatin peak at their 5-prime ends, which contains a single E2F binding site motif. Polycistronic genes do not appear enriched for either male or female exclusive genes. This study elucidates a potentially complex layer of gene regulation with distinct chromatin accessibility akin to monocistronic transcripts. This is the first report of polycistronic transcription in an apicomplexan and expands our understanding of gene expression strategies in this medically important organism.

Jessie Kissinger is a molecular evolutionary biologist who studies nuclear and organellar genome evolution in apicomplexan protist pathogens. She focuses on genome streamlining, genome organization, transfers of DNA between organellar and  nuclear genomes and horizontal gene transfer. More recently, her group has been studying gene regulation, non-coding RNAs and the population genomics of Cryptosporidium. She was a co-developer of PlasmoDB.org and related knowledgebases, VEuPathDB.org, and she was a member of its leadership team for over 20 years. Dr. Kissinger is a Distinguished Professor of Genetics and member of the Center for Tropical and Emerging Global Diseases at the University of Georgia.

Davis Auditorium

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