27 April 2021, 14:00, Virtual Seminar
Adam Pickard "A non-canonical secretory route for collagen assembly".
Adam is a senior postdoc in Karl Kadler’s lab (Wellcome Centre for Cell-Matrix Research, University of Manchester) studying how cells assemble a collagen-rich extracellular matrix. Published findings from our lab show that cells assemble collagen fibrils under circadian clock control, and that disruption of the clock produces abnormal fibrils that accumulate in numbers. However, earlier work published in 2004 from the Kadler group showed that cells in vivo can secrete procollagen within minutes. My recent work has focused on reconciling these apparently contradictory observations. In his talk, Adam will explain how he has used CRISPR-Cas9 editing and cell culture models to identify a non-classical secretory pathway of collagen secretion. His work has identified an unexpected role of lysosomal compartments in collagen secretion. These observations have relevance to fibrosis, in which uncontrolled deposition of collagen leads can cause death. He with new approaches, using nanoluciferase, to screen for collagen modulatory compounds.
Joan Chang “Understanding the role of endosomal recycling in collagen-I fibril formation”
Joan received her PhD in cancer studies from the lab of Janine Erler (Institute of Cancer Research, University of London), then went on to study adipocytes in the tumour microenvironment at UNC Chapel Hill with Dr Andrew Dudley. In 2016 Joan moved to Karl Kadler's lab where she made discoveries concerning the circadian regulation of collagen fibril assembly. Her recent work is showing that a crucial step in this process is uptake of collagen via the endosomal system. In her talk, Joan will show her recent data on endosomal trafficking using mass spectrometry and a novel method of fluorescence activated sorting of transport vesicles.
Richa Garva “To understand the role of type I collagen in determining cell fate, with translational opportunities for osteoarthritis"
Like Adam and Joan, Richa is a senior postdoc in Karl's lab. Richa approached the question of the purpose of the circadian collagen seen in adult mouse tendon by preforming a conditional knockout of col1a1 by crossing Col1a2CreERT2 and Col1a1-floxed mice, and feeding tamoxifen postnatally. To her surprise, fibroblasts that cannot synthesise col1a1 (and therefore cannot make collagen-I) switch to making collagen-II and express other chondrogenic markers including aggrecan, Sox9 etc. These data hint at a new role for Col1a1 in determining cell fate, and open up potential strategies for treating osteoarthritis.
Part of BRS Webinar Series