The kidney slit diaphragm looks like a fishnet | Biophysics Workshops in South Africa

The kidney slit diaphragm looks like a fishnet


Abstract

A comprehensive understanding of the molecular architecture of the slit diaphragm (SD), a critical component of the glomerular filtration barrier, is essential in elucidating renal filtration physiology and the mechanisms underlying kidney disease. Disruption of the SD is a hallmark of all forms of glomerulopathies, regardless of whether the cause is genetic, immunological, metabolic, or vascular. Our recent work demonstrated that the SD architecture in mice and Drosophila resembles a fishnet, with species-specific structural adaptations. Data on the near-native in-situ architecture of the human SD visualized at an unprecedented resolution through cryo-electron tomography of human kidney tissue shows that human Nephrin–Neph1 heterodimers are packed more closely than those in mice and in Drosophila, likely enhancing the permselectivity as the passage of filtrates is more restricted. Importantly, our ability to analyze native human tissue (without chemical fixation or staining) at a nanometer resolution enables physiological studies and mechanistic insight. This opens new opportunities for the in situ investigation of disease mechanisms and therapeutic development.

Hosted by Dr Jeremy Woodward

Speaker

Prof. Dr Achilleas Frangakis

Buchmann Institute for Molecular Life Sciences, Goethe University Frankfurt, Germany

About

Prof. Dr. Achilleas Frangakis is the Director of the Buchmann Institute for Molecular Life Sciences at Goethe University Frankfurt and a member of the Cluster of Excellence “SCALE.” Born in Athens, he moved to Germany in 1998 to pursue his PhD at the Max Planck Institute of Biochemistry in Munich. In 2002, he began a postdoctoral fellowship at Caltech in Pasadena, California, before becoming a group leader at the European Molecular Biology Laboratory (EMBL) in Heidelberg. Since 2008, he has held a professorship in Cryo-Electron Microscopy and serves as Head of the Center for Electron Microscopy at Goethe University Frankfurt.