Centre for Cancer Biomarkers CCBIO
CCBIO Seminar series

CCBIO Seminar – Karl Kadler

Welcome to a CCBIO Seminar with invited speaker Professor Karl Kadler, Director at the Wellcome Trust Centre for Cell-Matrix Research, Manchester, UK.

The seminar is open to all and includes a pizza get-together following the seminar. No registration needed.

Time: Thursday September 26th at 14:30.

Place: Auditorium 4, BB-building

SpeakerProfessor Karl Kadler, Director at the Wellcome Trust Centre for Cell-Matrix Research, Manchester, UK.

Title: "Circadian control of the secretory pathway is a central mechanism in tissue homeostasis"

Abstract: Collagen is the most abundant secreted protein in vertebrates and persists throughout life without renewal. The permanency of collagen networks contrasts with continued collagen synthesis throughout adulthood and with conventional transcriptional/translational homeostatic mechanisms that replace damaged proteins with new copies. Here we show circadian clock regulation of ER-to-plasma membrane procollagen transport by sequential rhythmic expression of SEC61, TANGO1, PDE4D and VPS33B. The result is nocturnal procollagen synthesis and daytime collagen fibril assembly in mice. Rhythmic collagen degradation by CTSK maintains collagen homeostasis. This circadian cycle of collagen synthesis and degradation affects a pool of newly-synthesized collagen whilst maintaining the persistent collagen network. Disabling the circadian clock causes abnormal collagen fibrils and collagen accumulation which is reduced in vitro by NR1D1 and CRY1/2 agonists SR9009 and KL001, respectively. In conclusion, our study has identified a circadian clock mechanism of protein homeostasis in which a sacrificial pool of collagen maintains tissue function.

Short bioKarl Kadler, PhD, is Professor of Biochemistry and Director of the Wellcome Centre for Cell-Matrix Research, University of Manchester.  His laboratory is focused on understanding how the collagenous scaffolds of most connective tissues are synthesised during skeletal development then maintained throughout life without renewal or turnover.  The prime example is tendon, in which the collagen has a half-life exceeding 200 years.  His talk will focus on a recent study, under review, that shows that the circadian clock regulates the daily synthesis and removal of a sacrificial pool of collagen that is needed for tissue integrity. A central mechanism is circadian clock regulation of the protein secretory pathway. His talk will include data from time-series transcriptomics and proteomics, super-resolution microscopy, volumetric electron microscopy, and conditional knockout mice. 

Chairperson: Donald Gullberg

The CCBIO Seminar series fulfills several aims.

  • Firstly, it conveys relevant biomarker research to the local scientific community and students and younger researchers in particular, providing the ground for future recruitment.
  • Secondly, it is part of two formal courses, BMED 380 on the master level, and together with the CCBIO Annual Symposium, forms CCBIO 902, a PhD level course.
  • Last, but not least, the CCBIO seminars with their subsequent open pizza get-together are an important arena for informal interaction between international researchers, CCBIO PIs and other CCBIO staff as well as interested researchers and students in general.

All interested researchers, students and others are welcome!