Modelling Metabolic and Signal Transduction Networks
1-4 September, 2004
St Hugh's College, Oxford, UK

Organisers:

Marta Cascante: University of Barcelona, Spain
David Fell: Oxford Brookes University, UK
Patti A. Quant: University of Oxford, UK

Report (draft)

Summary

This was a training course largely funded by the ESF Programme on Integrated Approaches to Functional Genomics. Additional sponsorship was provided by the EU SYMBIONIC network. The course was designed for predoctoral research students and post-doctoral researchers within one or two years of their doctorate. The course was organised by Marta Cascante (University of Barcelona), Patti Quant (University of Oxford), and David Fell (Oxford Brookes University), with assistance from Mark Poolman (Oxford Brookes University), Fernando Ortega (University of Barcelona) and Heike Assmus (Oxford Brookes University).

Course content covered in silico methods for the description of cellular systems by data and literature mining, predictions and simulations. The Symbionic-sponsored session covered the specific application area of the neuron. One aim of this course was to provide basic tools and concepts that would help students to acquire the skills in constructing step by step "cell simulators", through hierarchical modelling of signal and metabolic networks. The course included practical sessions on the use of computer tools specifically designed to handle problems such as modelling of metabolic and signal transduction. All participants gave a short oral description of their work, and many submitted a poster.

21 students were given sponsored places on the course and a further 13 attended paying a registration fee.

Scientific content

The course started with sessions on the mathematical representation of enzyme kinetics and metabolic networks as the first steps in the modelling of metabolism. This was followed by a session on metabolic control analysis, which introduces the concept of the sensitivity of metabolic variables to enzyme activities. This then formed the subject matter of the first of the practical computer sessions. Students followed exercises in the simulation of a simple metabolic system and exploring its flux control coefficients. This material was presented at a beginners' level using the Windows-based simulation program Gepasi and at a more advanced level for those who already had some experience of metabolic modelling using the Python-based package ScrumPy running on Linux workstations.

The next lecture session on protein-protein interactions and databases introduced one of the strands in the second round of computer sessions; students spent half their time on a database exercise, and half continuing the simulation exercises they had started the day before.

The lecture programme continued with modelling the neuronal cell as a specific case study, with some of the lecturers sponsored by the SYMBIONIC Framework 6 network that has this as its goal.

The remainder of the lecture programme used some selected elements from the opening sessions of the 11th Biothermokinetics Workshop. Jacky Snoep's plenary lecture considered the new challenges for theoretical and computational biology arising from the growing interest in the emerging field of systems biology. This was followed by accounts of new tools for metabolic modelling, and the closing sessions covered examples of modelling signal transduction and metabolic pathways.

Throughout the programme there were sessions where students on the course gave short accounts of their projects, reporting on where they were already using, or planning to use, modelling approaches. Many of these presentations were supported by a poster, and a poster-viewing session was included.

The final evening of the course included a student-only session, which was a self-organised discussion amongst the students, but which also was tasked with providing feedback on the course. (The outcomes are discussed below.)

The course was accompanied by a 52 page booklet containing course materials, notes, practical instructions and exercises.

Discussion

Overall, the course was regarded as being at an appropriate level and depth according to the student feedback, though it was felt that the timetable was intense and over-full. The students would have liked more time for discussions between themselves. It was also felt that probably the student body was too diverse and that it would be better providing separate events for beginners (whether doctoral students at the start of their project, or experienced researchers moving into modelling for the first time) and those who already had projects under way. They would also have liked the student presentation sessions to be less formal, for example chaired by the students themselves, though with senior researchers present to provide comments and feedback. The main suggestion for an addition to the course was more application-focussed lectures, to give an idea of the potential of modelling approaches, as well as the didactic material. (It should be noted, however, that the final sessions of the course, which were the morning after the feedback session, were mainly applications talks.)

In conclusion, it has been demonstrated that there is sufficient demand, Europe-wide, for a course of this type, and after an appropriate interval to allow a new cohort to come through (two years?), it should be viable to repeat it, building on the material developed for this run. However, the length of the course should be extended to four full days, without addition of much extra material.

List of participants

Speakers
Prof. Luis Acerenza : Faculty of Science, Uruguay (on sabbatical at University of Barcelona at the time)
Dr. Ivan Arisi : PKO- Bioinformatics, Lay Line Genomics, Italy
Prof. Marta Cascante : Biochemistry and Mol. BIol., University of Barcelona, Spain
Prof. David Fell : Biological & Molecular Sciences, Oxford Brookes University, UK
Prof. Reinhart Heinrich : Institute of Biology, Theoretical Biophysics, Humboldt University Berlin, Germany
Prof. Jan-Hendrik Hofmeyr : Biochemistry, University of Stellenbosch, South Africa (on sabbatical at the University of Amsterdam at the time)
Mr. Fernando Ortega : Bioquimica i Biologia Molecular, Universitat de Barcelona, Spain
Dr. Mark Poolman : Biological & Molecular Science, Oxford Brookes University, UK
Dr. Patti Quant : Department of Biochemistry, University of Oxford, UK
Prof. Jacky Snoep : Biochemistry, University of Stellenbosch, South Africa
Prof. Alfonso Valencia: Protein Design Group, Centro Nacional de Biotecnologia, Spain
Dr. Michel Kerszberg:, University Pierre and Marie Curie, France
Dr. Nicolas Le Novère:, European Bioinformatics Institute, UK

Participants
Miss Gema Alcarraz : Biochemistry and Molecular Biology, University of Barcelona, Spain
Miss Heike Assmus : Biological & Molecular Sciences, Oxford Brookes University, UK
Mr. Bhushan Bonde : Biological & Molecular Sciences, Oxford Brookes University, UK
Mr. Daniel Brewer : CoMPLEX and Institute of Child Health, University College London, UK
Dr. Keira Curtis : Clinical Biochemistry, University of Cambridge, UK
Mr. Martin Grana : , Institut Pasteur, France
Mr. Jurgen Haanstra : Molecular Cell Physiology, Vrije Universiteit Amsterdam, the Netherlands
Mr. Soren Helmark : Biocentrum, Technical University of Denmark, Denmark
Dr. Dagmar Iber : CMB, Mathematical Institute, UK
Miss Beate Knoke : Bioinformatics, University of Jena, Germany
Mr. Ilkem Emrah Nikerel : Dept. of Biotechnology, TU Delft, The Netherlands
Miss Judit Oláh : Institute of Enzymology, Hungary
Mr. Nicolas Parisey : Physiology Mitochondria Laboratory, Victor Segalen University, France
Mr. Harshil Patel : Biological & Molecular Sciences, Oxford Brookes University, UK
Mr Asad Rahman: CUBIC, University of Cologne, Germany
Mr. Michael Rempel : Mathem. Nat. Department, HU Berlin, Germany
Mr. Fernando Jesús Reyes Zurita : Biochemestry and Molecular Biology, University of Granada, Spain
Mr. Juan-Carlos Rodriguez : Biochemistry and Molecular Biology, University of Barcelone, Spain
Mr. Sergio Rossell : Molecular Cell Physiology, Vrije Universiteit, The Netherlands
Mr. Pedro Vizan : Biochemistry and Molecular Biology, University of Barcelona, Spain
Mr. Mikhail Paveliev : Institute of Biotechnology, University of Helsinki , Finland
Dr Mathew Cheetham: Chemistry, University of Southampton, UK
Dr. Martino Barenco : CoMPLEX, University College London, UK
Miss Jildau Bouwman : Molecular Cell Physiology, Vrije Universiteit Amsterdam, The Netherlands
Mr. David Mendoza-Cozatl : Biochemistry, Instituto Nacional de Cardiologia, Mexico
Miss Ana Paula Oliveira : BioCentrum, Technical University of Denmark, Denmark
Miss Sabine Peres : Universite Bordeaux 2, Laboratoire physiologie mitochondriale, France
Dr. Che Pillay : Biochemistry, University of Stellenbosch, South Africa
Dr. Paola Roncaglia : Neurobiology, SISSA-ISAS , Italy
Mr. Parag Saudagar : Food & Fermentation Technology, U.I.C.T., India
Mr. Christopher Snell : Physiomics plc, UK
Mr Ake Johannes Vastermark: Staistics, University of Oxford, UK
Miss Cathy Vermont : Physiomics plc, UK
Dr. Ionela Zevedei-Oancea : Theoretical Biophysics, Humboldt University Berlin, Germany