Archive for August, 2018

SIAM Life Science Conference in Minneapolis

August 11, 2018

Here are some impressions from the SIAM Life Science Conference. On Monay I heard a talk by Nathan Kutz about the structure and function of neural networks in C. elegans and a moth whose name I have forgotten. Coincidentally, when I was in Boston I heard a presentation by someone in the Gunawardena group about genes and transcription factors related to different types of neurons in C. elegans. On that occasion I asked how many of the few hundred neurons of C. elegans are regarded as being of different types and I was suprised to hear that it of the order of one hundred. Returning to the talk of Kutz, the key thing is that all the neurons in C. elegans and all their connections are known. Thus it is possible to simulate the whole network and reproduce central aspects of the behaviour of the worm. Another simplifying circumstance is that the motion of the worm can be described by only four parameters. A central message of the talk was that the behaviour of the nervous system of the worm itself can be reduced to a low dimensional dynamical system. This reminded me, with how much justification I do not know, of what I heard about the beaks of Darwin’s finches in Lisbon recently. As for the moth, the question described in the talk was how it learns to identify odours. A lot is known about the architecture of the neurons in the moth’s olfactory system. The speaker has compared the learning ability of this biological neural network with that of artifical neural networks used in machine learning. In reaching quite a high accuracy (70%) on the basis a small amount of training data the moth network beat all the artifical networks clearly. When given more data the result of the moth network hardly improved while those of the artificial network got better and better and eventually overtook the moth. The speaker suggested that the moth system is very effectively optimized for the task it is supposed to perform. I also heard a nice talk by Richard Bertram about canards in a three-dimensional ODE system describing the electrical activity of heart cells. I found what he explained about canards enlightening and this has convinced me that it is time for me to finally understand this subject properly. In particular he explained that the oscillations associated with a canard have to do with twisting of the stable and unstable manifolds. I also found what he said about the relations between the canard and concrete biological observations (the form of electrical signals from neurons) very interesting.

On Wednesday I heard a talk by Benjamin Ribba, who after an academic past now works with Roche. One of the main themes of his talk was cancer immunotherapy but I did not feel I learned too much there. What I found more interesting was what he said in the first part of his talk about chemotherapy for low-grade glioma. This is a disease which only develops very slowly, so that even after it has been discovered the tumour may grow very slowly over a period of several years. He showed patient data for this. He explained why it was reasonable to leave patients so long without therapy. The reason is that the standard course of therapy at that time was something which could only be given to a patient once in a lifetime (presumably due to side effects). Thus it made sense to wait with the therapy until the time which was likely to increase the patients lifetime as much as possible. During the slow growth phase the disease is typically asymptomatic, so that it is not a question of years of physical suffering for the patient. The speaker develeloped a mathematical model for the evolution of the disease (a model with a few ODE) and this could be made to fit the data well. The time course of the tumour growth is as follows. Before treatment it grows steadily. After the treatment is started the tumour starts to shrink. After the treatment is stopped it continues to shrink for a long time but usually eventually takes off again after a few years. In the model it was possible to try out alternatives to the standard treatment protocol and one was found which performed a lot better. The talk did not include any indication of whether this information had been used in paractise. I asked that question at the end of the talk. The answer was that by the time the analysis had been done the standard treatment has been replaced by a very different one and so the theory was too late to have clinical consequences.

On Thursday I heard a talk by Dominik Wodarz. One of his themes was oncolytic viruses but here I want to concentrate on another one. This had to do with chronic lymphocytic leukemia. This is a B cell malignancy and is treated using ibrutinib, an inhibitor of BTK (Bruton’s tyrosine kinase). Most of the malignant B cells form a tumour in the bone marrow while a small percentage of them circulate in the blood. Measuring the latter is the easiest way of monitoring the course of the disease. When the drug is given the tumour shrinks but it was not clear whether this is because the cells leave the bone marrow for the blood, where they die, or whether a large proportion die in the marrow. Using a simple mathematical model it could be shown that the second of these is the correct explanation. There are several things I like about this work. First, very simple models are used. Second, after comparison with data, these give convincing explanations for what is happening. Third, these conclusions may actually influence clinical practise. This is a good example of what mathematical biology should be like.

Visit to Boston

August 5, 2018

At the moment I am visiting Boston for the first time in my life. On Thursday I gave a talk at Harvard Medical School, at the invitation of Jeremy Gunawardena. The fact was not lost on me that this address was a quite exceptional one among the long list of places where I have given talks in my life. The subject of my talk was T cell signalling and, in particular, my work on this with Eduardo Sontag. I had a look around in the surrounding area and was impressed to see the variety of prestigious medical institutions which I knew by reputation, such as the Boston Children’s Hospital, The Dana-Farber Cancer Center and the Brigham and Women’s Hospital. I was happy how many pedestrians there were, indicating that at least in Boston the pedestrian is not an endangered species.

On Friday I gave a talk on T cell activation at Northeastern University at the invitation of Eduardo Sontag. This is an institution which has recently jumped up in the rankings by cutting its student numbers drastically and increasing its fees correspondingly. The basic subject of the talk was the same as on Thursday but it was modified in order to try to cater for a different audience. The talk on Friday included more mathematics (since I expected that on average the Friday audience would have a stronger mathematical background than that on Thursday) and more biology (since on Thursday I left out more of the biology which I assumed would be known to most of the audience). There were two other talks by Michael Margaliot and Yoram Zarai. They were on the subject of certain models for the way that ribosomes are allocated to mRNA. A key idea is that many ribosomes moving along an RNA molecule could get into traffic jams. Indeed there is a close relation between these and models for traffic jams in the literal sense. The question is then how the machinery of the cell should be organized to avoid such traffic jams. Typical mathematical techniques which were applied in the work explained in the talk were theorems about monotone systems of ODE (or corresponding control systems) satisfying some extra conditions leading to a simplification of their dynamics.

Today, Saturday, I spent most of the day walking around in Boston and Cambridge. In the morning it rained quite a bit but with an umbrella that was no problem. I was blissfully unaware of the fact that there had been a tornado warning and I also only heard later that a tornado did today hit a place not too far from Boston. In Cambridge I observed a turkey sitting on the pavement and looking into a shop window as if it was considering what it might buy. After a while it crossed the road and seemed to be well-educated since it was very careful to stay on the zebra crossing. By chance and without expecting anything special I happened to enter the palatial Boston Public Library. Later in the afternoon I was on the waterfront near the aquarium and the pleasant experience of sitting by the sea was heightened by the fact that the gull on top of the lamppost was a Ring-Billed Gull, a treat for my European eyes. I also spontaneously decided to take a boat trip around the harbour. In coming to Boston I had no special expectations about the city itself. Despite my short and superficial acquaintance with the place I can say that it has gained a secure place on my personal list of the most attractive cities I know.