"Establishing Causality in Microbiota Research" 

by Dr. Volker Mai, Department of Epidemiology, University of Florida

Jennifer Kurasz of the Karls Lab is the recipient of the 2020 Dr. Juergen Wiegel Award.  The award was announced on February 25, 2021 at the Dr. Juergen Wiegel seminar. The Dr. Juergen Wiegel Graduate Award in Microbiology was established by Dr. Wiegel, his family, and his former students and colleagues.  This award recognizes graduate students for excellent work in non-medical microbial biodiversity and microbial physiology.  Congratulations Jenn!

Abstract: Cilia and eukaryotic flagella are slender cell projections with motile and sensory functions. They lack ribosomes and all ciliary building blocks need to be imported posttranslationally from the cell body. This task involves intraflagellar transport (IFT), a motor-based protein shuttle. Using single particle imaging in the unicellular alga Chlamydomonas reinhardtii, we determined key aspects of ciliary protein transport such as cargoes and unloading sites. The transport frequencies of structural proteins such as tubulin are upregulated when a cilium is too short revealing that cells sense the length of their cilia and adjust the cargo load of IFT, accordingly. In mammals, cilia malfunction leads to a plethora of diseases, named ciliopathies. Many of the disease-related proteins are conserved in protists. Biochemical analyses of isolated Chlamydomonas cilia and live imaging revealed that the BBSome, an octameric protein complex, is an adapter mediating the export of certain signaling proteins from cilia by IFT. This led to the concept that Bardet-Biedl syndrome (BBS, characterized by obesity, kidney anomalies, polydactyly and blindness) results from the abnormal accumulation of (signaling) proteins in cilia. One of the most common inherited single-gene, life-threatening disorders is autosomal dominate polycystic kidney disease (ADPKD), which affects ~1:1,000 adults. ADPKD results from mutations in the TRP cation channel PKD2, but the role of PKD2 in cilia remains unclear. In Chlamydomonas, PKD2 anchors the mastigonemes, large extracellular glycoprotein polymers, to the ciliary membrane. The PKD2-mastigoneme complexes are arranged in two rows along the axoneme positioning them perpendicular to the plane of the ciliary beating. Association with extracellular components, the cytoskeleton or both is characteristic for many mechanically gated channels in eukaryotes. We proposed that pull on these polymers during bending of the axoneme could generate a force to open the PKD2 channel.

The department will be hosting UGA MIBO alum, Dr. Volker Mai (worked in Juergen Wiegel’s lab), to give a seminar this month (Thurs, Feb 25 – seminar at 11:10am) to celebrate announcing the winner of the 2020 Wiegel Award!

Dr. Volker Mai, Department of Epidemiology, University of Florida

Over the last two decades, the role of the commensal microbiota in human health has received enormous research interest. There has been significant progress in detailing the composition and activities of the microbiota at various anatomic sites and correlating distortions in microbiota with various health and disease endpoints. However, to date there appears to be a sparsity of evidence sufficient to support a causal contribution of microbiota to human health and disease. Establishing causality, beyond simple correlations, is crucial for the future development of microbiota targeting prevention regimen. Using examples from our microbiota research I will elaborate on these concepts and discuss potential approaches to advance the field.