BBSRC Systems Biology Grantholder Workshop, University of Nottingham, 16 December 2008.
Michael White: Dynamics and function of the NF-kappaB signalling system. NF-kappaB controls cell division and cell death in all cells. How can a simple signal carry so much information (the cell cannot afford to make a mistake!)? It is a complex network with multiple feedback loops (high dynamic complexity). People think that the IkappaB holds it in the cytoplasm, but this doesn't look to be correct. Living cell imaging shows that NF-kappaB oscillates asynchronously between the cytoplasm and nucleus in single cells (i.e. doesn't happen at the same time in multiple cells). However, each cell is cycling with the same amplitude etc, so they're doing the same thing, just not at the same time.
Can we synchronise the oscillations? You can do a repeat pulse protocol and then check to see if the synchronisation has happened. When you stimulate at 100-150 minutes then you can synchronise and not get damped oscillations. They have built a stochastic model. There are a nice set of pictures of pathways, but obviously cannot reproduce those here.
Here go the batteries again…(rest of notes from the paper notes I took, which are generally much lower quality)
Some of this work is funded under SABR, where they will focus on dynamic live cell imaging, quantitative proteomics/phosphoproteomics, genomics/bioinformatics, data analysis, deterministic/stochastic modelling and databases. What are the causes of differential expression? Oscillation dynamics is one possibility (and what he describes in this talk) Others could be signal-specific IkappaB processing, differential NF-kappaB dimer formation, differential protein modifications. Is degradation of IkappaBs regulated by Rel protein binding? NF-kappaB could be differentially phosphorylated.
Finally, one last note on outreach: they've had quite the success with biologists interacting with mathematicians in the group. Biologists are now taking weekly math courses, and it was their idea. That's great 🙂
These are just my notes and are not guaranteed to be correct. Please feel free to let me know about any errors, which are all my fault and not the fault of the speaker. 🙂