Judith and David Coffey Seminar: Prof Marc Wilkins (UNSW)

Title: Systems or sub-systems biology? Which can best help us understand the cell? 

Abstract: The promise of systems biology is that the study of a cell, via its components
and their interactions, will define and reveal emergent properties of that system.  The
use of large-scale 'omics techniques is essential for this, however many such
techniques still cannot measure all relevant biomolecules and their interactions.  This
leaves us with an incomplete and sometimes shallow understanding.  This talk will
describe our research into two, tractable sub-systems of the cell where we have sought
to fully define their components, interactions and aspects of function.  

First, I will describe our work to fully define the ‘protein methylation network' of
a eukaryotic cell.  Here, we asked is it possible to identify all instances of a
post-translational modification in a eukaryote? We also asked, can we prove it? We then
asked can we define all enzymes, in this case methytransferases, that are responsible
for this modification – and in doing so construct a complete sub-system in the cell.
We have been successful in addressing the above, which has allowed a range of emergent
properties of this network to be discovered.  

Secondly, I will describe our work to understand how two regulatory subsystems in the
cell - the signalling system and the histone methylation system - actually connect.
In yeast, four enzymes methylate histones and four can demethylate histones.  They do so
with remarkable precision and dynamism, helping define regions of the genome to be
transcribed.  We asked are these enzymes phosphorylated, and to what degree? We also
asked are phosphosites associated with specific cellular responses; in effect do certain
phosphorylation events on the histone methylating enzymes direct them to change
chromatin in certain parts of the genome? We additionally asked can we find which
kinases are responsible; thus connecting the sensing / signalling system with that of
chromatin regulation? This story is less complete than that above, but is compelling! 

About the speaker: Marc is a professor of systems biology and is deputy dean (research
and enterprise) in the faculty of science at UNSW.  He has had a longstanding interest
in understanding cells at a systems level, and finding ways to do that.  He defined the
concept of the proteome, coined the term, and has directed entities such as the Systems
Biology Initiative (SBI) and the Ramaciotti Centre for Genomics (2011-2022).  He is
currently the UNSW node leader in the MACSYS ARC Centre of Excellence, which has the
goal of building mathematical and computational models of whole cells.  

Marc has a career output of >280 publications in proteomics, especially concerning
protein post-translational modifications, and in genomics, transcriptomics and
biological networks.  In industry, Prof.  Wilkins co-founded two biotechnology
companies, both which took products to market and which were ASX-listed.  Proteome
Systems had a focus on proteomic technology development and its application to
biodiscovery.  Regeneus (now Cambium Bio) developed cell-based therapies for the
treatment of inflammatory conditions.