A Report on
Workshop on Mathematical & Computational Biology

Centre for Cellular & Molecular Biology,
January 8 -13, 2001, Hyderabad, India

Somdatta Sinha, CCMB, Hyderabad and Philip K. Maini, Oxford.

Application of mathematical and computational analyses to describe the structure and function of complex biological systems is an emerging area of study. The role in describing patterns and processes in cellular and molecular biology is assuming greater importance with the fast emerging information of genome sequences in a variety of organisms, including the human. On the other hand, conceptual advancements in physical theory of complex systems are increasingly playing significant roles in describing emergent biological processes.

In India, many people are armed with methodologies specific to their own field of work in both biological and physical sciences, yet a close communication leading to an interdisciplinary description of the natural world is not forthcoming. The need is felt to have discussions encompassing a larger canvas to expose the commonalties across the boundaries of individual disciplines and to use the powerful tools available in each discipline to arrive at a coherent description of nature. We feel that one way to promote changes in the desired direction is to make students and young researchers in different fields of inquiry aware of the power of interdisciplinary research by exposing them to theoretical treatment of specific biological problems. This is also one of the aims of the World Outreach Committee (WOC) of the Society for Mathematical Biology, which was formed to encourage activities in mathematical biology in different parts of the world.

One of the undersigned, Dr. Somdatta Sinha, also a member of the WOC, proposed to hold a Workshop on Mathematical and Computational Biology in India for students and young researchers in different disciplines of science which would consider specific problems in a few selected areas in biology and, in the process, expose participants to the variety of mathematical and theoretical approaches that are used to study them. The response of the SMB was very encouraging and they offered support with a grant of $1000 to enable participation of students.

This workshop was the first of its kind in India and was held at the Centre for Cellular & Molecular Biology (CCMB), a premier national laboratory of the Government of India engaged in research in modern biology, during January 8-13, 2001 in Hyderabad, India. It comprised five faculty and two associate faculty members (four from USA, two from UK and one from India); seven computational laboratory associates (all from CCMB), and forty participants (10 females and 30 males) selected from over 70 applicants.

The participants came from diverse scientific backgrounds (e.g., biochemistry, microbiology, agriculture, veterinary science, physics, mathematics, engineering, biotechnology and zoology), from 24 different institutes, universities and engineering colleges in India, and ranging from undergraduate level to junior faculty. Everyone was received at the railway station or airport and housed at the very comfortable guest house of the CCMB, which is two minutes walk from the lecture theatre in the main research building. The lecture hall was adequately equipped, catering to the lecturers needs for electronic or conventional modes of display.

The programme started on the evening of the 7th with registration of participants and a mixer followed by dinner where the participants met the faculty and organisers. The workshop started on the morning of the 8th. There were five course modules, each lasting one day. Each module consisted of three one hour lectures in the morning, followed by a computer 'lab' in the afternoon lasting 4-6 hours. Participants worked in pairs (per computer) during the lab and tackled exercises designed to reinforce the mathematical and computational concepts introduced in the lectures. Advanced exercises were set to challenge the more mathematically sophisticated participants. The faculty, along with the computer lab associates, discussed specific issues with participants and provided general help during this session. Each participant was given a workbook which had an impressive compilation of relevant articles for each module chosen by the faculty along with some introductory material on the lectures. All required software was downloaded, and available on all (twenty) computers which were networked with internet and telnet connections.

The first module was entitled "Modeling and analysis of large scale gene expression data" and was given by Andreas Wagner (Department of Biology, University of New Mexico, USA). It described a number of experimental techniques for measuring single and large scale gene expression, and the statistical and computational approaches used to analyse the data obtained. Methodologies used for data pre-processing and a variety of hierarchical and non-hierarchical clustering algorithms were discussed that gave a clear overview of the importance of theoretical studies in the area.

The second module, "Ionic models and the physiology of electrically excitable cells", was given by Arthur T. Sherman (Mathematical Research Branch, NIDDK, NIH, USA). It consisted of an introduction to cell electrophysiology, with particular application to modeling the bursting dynamics of the pancreatic beta cell that secretes insulin in response to glucose. Classical ordinary differential equation (ODE) models describing the temporal dynamics of ionic currents were derived, linear stability and phase plane analysis discussed, and time evolution profiles studied.

Spatiotemporal patterns were introduced by Philip K. Maini (Mathematical Institute, Oxford University, UK) in the module, "Pattern formation in development", which explored the phenomenon of self-organisation in Turing structures and cellular slime mould using partial differential equation (PDE) models. Given the mathematical nature of the topic and non-mathematical background of a large number of participants, he developed the theory from first principles which he then illustrated in the afternoon's computer exercises.

Pejman Rohani (Zoology Department, Cambridge University, UK) derived ODE models of the SEIR type for microparasite infections in his module, "Models in epidemiology". He analysed the models for measles and whooping cough, and carried out detailed comparison with data for England and Wales, both before and after vaccination. He also introduced stochasticity, spatial effects, and investigated interactions between diseases (interference). He stressed the need to consider mathematical modelling as a means to reveal the underlying dynamics in data.

The final module, "Sequence analysis and phylogenetic trees", given by Catherine Macken (Theoretical Biology & Biophysics, Los Alamos Laboratory, USA) introduced the concept of alignment and methods for comparing different DNA and protein sequences. Techniques for constructing the most likely phylogenetic tree, based on the given sequences, were introduced and the Maximum Likelihood Approach was discussed in detail. She applied the concepts in the context of evolution of the influenza virus and development of the flu vaccine.

As well as learning a range of mathematical techniques and biological background on a variety of problems, the students were exposed to a diverse number of computational tools; for example, XPP, FORTRAN programmes for studying PDEs, various packages for sequence alignment and statistical analyses for cluster analysis and phylogenetic analysis.

The participants were very motivated and enthusiastically grabbed the opportunity to discuss concepts and problems with a very helpful faculty. The set-up, with buffet lunches, dinner, and coffee/tea together on the roof terrace (offering splendid views of the twin cities of Hyderabad and Secunderabad) afforded easy mixing and communication. At times the participants became so engrossed in the lab that they had to be prised from their computers and ordered to take a coffee break! Everybody found the food truly wonderful and the biscuits (baked in the canteen of CCMB) were addictive. The CCMB was a welcoming host and the Director organised a special rooftop dinner on the11th affording people the chance to meet with experimental scientists from the Institute. The organisers took very detailed feedback from both the faculty and participants for information which will help in organising future events of this kind.

The funding from the SMB allowed the organisers to support registration fees for 12 and travel for 9 participants. It also helped defray the cost of accommodation and food for the participants.

Support was also available from local governmental bodies such as the Department of Biotechnology, Indian Council of Medical Research, and Council of Scientific and Industrial Research, India

On the last day there was a concluding session where the Certificates of Attendance were presented to the participants and they expressed their view about the workshop. Judging from the responses of the participants, the workshop was a tremendous success. Both the biologists and physical scientists learned from the course and it seemed that the workshop helped reduce the gap between them as they felt that the interdisciplinary approach was important in studying biological systems. This made both the faculty and the organisers feel that the whole activity was worth the months of effort that they had put in. The workshop ended with a tour of Hyderabad and a "Sound & Light Show" in the historic fort of Golconda.