Systems and synthetic biology in Strasbourg

This past week I was at a conference entitled ‘Advances in Systems and Synthetic Biology’ in Strasbourg. The first talk was by Albert Goldbeter and anyone who has read many of the posts on my blog will realize that I went there with high expectations. I was not disappointed. It was a broad talk with the main examples being glycolysis, circadian rhythms and the cell cycle. A lot of the things he talked about were already rather familiar. It was nevertheless rewarding to hear the inside story. There were also enough themes in the talk which were quite new to me. For instance he mentioned that oscillations have been observed in red blood cells, where transcription is ruled out. I enjoyed listening to him, perhaps even more than I did reading his book. Another talk on Monday was by Jacques Demongeot. I am sure that he is a brilliant, versatile and highly knowledgeable person. Unfortunately he made no concessions in his talk for the benefit of non-experts. He jumped into the talk without saying where it was going and I did not have the background knowledge to be able to supply that information on my own. I felt as if I was flattened by a blast wave of information and unfortunately I understood essentially nothing.

The first talk on Tuesday was by Nicolas Le Novère and it had to do with engineering-type approaches to molecular biology. This is very far from my world but gave me some fascinating glimpses as to how this kind of thing works. Incidentally, I found out that Le Novère has a blog with a number of contributions which I found enlightening. The next talk was by François Fages and was focussed on computer science issues. It nevertheless contained more than one aspect which I found very interesting. At this point I should give some background. There are influential ideas on the relation of feedback loops to the qualitative behaviour of the solutions of dynamical systems due to René Thomas. They have been developed over many years by several people and a number of them are at this conference (El Houssine Snoussi, Marcelle Kaufman, Jacques Demongeot) and today I attended a tutorial held by Gilles Bernot on related themes. The basic idea is ‘positive feedback loops are necessary for bistability, negative feedback loops for periodic solutions’. I will not get into this more deeply here but I will just mention that some of the conjectures of Thomas have been made into theorems over the years. For instance a rather definitive version of the result on multistability was proved by Christophe Soulé. In his talk Fages mentioned a recent generalization of this result due to Sylvain Soliman. In the past I had the suspicion that the interest of the conjectures of Thomas was severely limited by the fact that the hypotheses rule out certain configurations which are very widespread in reaction networks of practical importance. It seemed to me that Fages made exactly this point and was saying that the improved results of Soliman overcome this difficulty. I must go into the matter in more detail as soon as I have time. Another point mentioned in the talk was an automated way to find siphons. This is a concept in reaction networks which I should know more about and I have the impression that in a couple of cases I have discovered these objects in examples without realizing that they were instances of this general concept.

On Wednesday there was an extended presentation by Oliver Ebenhöh. One speaker had cancelled and Oliver extended his presentation to fill the resulting extra time. I felt that listening to the presentation was time well spent and I did not feel my attention waning. He explained many things related to plant science and, in particular, the use of starch by plants. One key topic was the way in which a particular enzyme acts on chains of glucose monomers (generalization of maltose, which is the case of two units). It creates a kind of maximal entropy distribution of different lengths. The talk presented both a theoretical analysis and precise experimental results. The theoretical part involved an application of elementary thermodynamic ideas. I liked this and it brought me to a realization about my relation to physics. In the past I have been exposed to too much theoretical physics of a very pure kind, remote from applications to phenomena close to everyday life. It was refreshing to see basic physical ideas being applied in a down to earth way to the analysis of real experiments, in this case in biology.

In his talk on Thursday Joel Bader talked about his work on engineering yeast in such a way as to find out which combinations of genes are essential for survival. The aim is to look for a kind of minimal genome within yeast. One of the techniques of gathering information is to do a random recombination using a Cre-Lox system and looking to see which of the mutants produced are viable. The analysis of these experiments leads to consideration of self-avoiding or non-self-avoiding random walks and at this point I had a strange feeling of deja vu. A few weeks ago I gave a talk in the Hausdorff colloquium in Bonn. In this event two speakers are invited on one afternoon and their themes are not necessarily correlated. On the day I was there the other speaker was Hugo Duminil-Copin and he was talking about self-avoiding random walks, a topic which I knew very little about. Now I was faced with (at least superficially) similar ideas in the context of DNA recombination. At the end of his talk Bader spent a few minutes on a quite different topic, namely bistability in the state of M. tuberculosis. I would have liked to have heard more about that. He is collaborating on this together with Denise Kirschner whose work on modelling tuberculosis I have discussed in a previous post.

This meeting had the advantages of relatively small conferences (in this case of the order of 50 participants) and has served the purpose of opening new perspectives for me.


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