Trento Centre: Award-Winning Research
March 26, 2009 3:21 PM PT

In February 2005, Bill Gates, Microsoft chairman, signed an agreement in Prague, along with two ministers of the Italian government, a councilor from the Italian province of Trento, and the rector of the University of Trento, to establish The Microsoft Research – University of Trento Centre for Computational and Systems Biology (CoSBi).

The centre, focused on the convergence of the life sciences and computer science, was established with a specific, far-reaching vision: to foster the development of “a new kind of scientist, empowered with novel conceptual and computational tools smoothly connecting models and experiments” to “discover and better understand fundamental biological principles at different levels, from molecular to ecological systems, and thereby construct a brighter future for the quality of our lives and our environment.”

Four years on, how has CoSBi fared in this ambitious undertaking?

The answer came Feb. 27 at the Leibniz-Zentrum für Informatik at Germany’s Schloss Dagstuhl, when CoSBi Lab, a software platform for biological modeling, analysis, and simulation, was named the winner of the first international competition on Formal Methods in Molecular Biology.

CoSBi building
A beautiful setting provides inspiration to CoSBi researchers.

“I am very pleased with the exceptional work that the CoSBi team is carrying out,” said Corrado Priami, president and chief executive officer of the centre. “The teamwork that was demonstrated throughout the preparation for the international competition is proof of the efforts we have put into creating a multidisciplinary and dynamic research centre at the convergence between computer science and life sciences.

“The prestigious award won in Dagstuhl recognizes the research undertaken at CoSBi, which has always concentrated on quality, not quantity,” Priami added. “CoSBi has consolidated its position at an international level as a point of reference for the new discipline of algorithmic systems biology, which has been developing rapidly in the last few years.”

Eleven of the centre’s researchers combined with three colleagues from France and one from Germany on the winning entry. Attila Csikász-Nagy, the team leader, hailed the triumph as evidence that the approach taken by the research facility is paying dividends.

“This victory,” Csikász-Nagy said, “is important evidence of how the methods that we are developing demonstrate their validity, especially in the field of biology.”

The researchers involved demonstrated how the models of the cell cycle—the 24 hours in which each cell duplicates itself—and the capacity of cells to distinguish day from night are not completely consistent with experimental data regarding mammalian cells. The team suggested modifications that could make the models more accurate and predictive, necessary to enable the study of chronotherapy, determining the best moment of the day to administer specific medicines.

Alessandro Romanel, the CoSBi researcher who represented the team in the Dagstuhl competition, expressed confidence in the efficacy of the CoSBi Lab techniques.

“The innovative instruments that we have developed at CoSBi,” Romanel said, “allow us to tackle new problems and, therefore, formulate new hypotheses on the function of the principal biological mechanisms that regulate the activities of human cells.”

Naturally, such achievements—and the validation supplied by the Leibniz event—have not escaped the attention of the leaders of both of the centre’s parent institutions.

“This external recognition for the work of the CoSBi is a true milestone for the centre,” said Andrew Herbert, managing director of Microsoft Research Cambridge, “and a step further toward fulfilling the founding vision to create a new breed of scientist equipped with the right tools to better understand biological science and help to tackle the world’s environmental problems.

“Our partnership with the University of Trento has been a longstanding and fruitful one, combining forces to further advance the study of computational science, in particular the intersection between life sciences and computer science, and we look forward to further success stories coming out of the lab.”

Davide Bassi, rector of the University of Trento, cited the benefits of a European public-private scientific venture.

“I am very proud of the work done at CoSBi, the first research centre in the world in which Microsoft shares its name with a third party, the University of Trento,” Bassi said. “We have succeeded in implementing that synergy between the private and public sectors in research that is lacking in Europe and is necessary to be competitive with other systems of research and which can be a strategic propeller for the economy, especially during difficult times such as the one in which we are currently living.

“One of the exceptional accomplishments of CoSBi is its ability to attract great talents from all over the world, in contrast to the traditional brain drain to which Italy and Europe are historically exposed.”

More than a hundred researchers from across the globe participated in the Schloss Dagstuhl event, designed to evaluate biological modeling and analysis techniques recently developed internationally.

CoSBi researchers who contributed to the effort, in addition to Csikász-Nagy and Romanel, included Ferenc Jordán, Roberto Larcher, Paola Lecca, Alida Palmisano, Sean Sedwards, Judit Zámborszky, Paolo Ballarini, Tommaso Mazza, and Ivan Mura.

They were joined by Sylvain Soliman, of INRIA Paris-Rocquencourt; Adrien Fauré, of Technologie Avancée pour la Génome et la Clinique, located in Marseille, France; Denis Thieffry, from the Université de la Méditerrannée - Aix-Marseille II; and Heike Siebert, from Freie Universität Berlin.

CoSBi Lab, based on the new programming language BlenX, is an effort to develop a complete artificial laboratory that can replicate via computer simulation all the activities usually performed in wet labs. The effort offers features to analyze the outcomes of simulations including main statistical techniques and visualizations of networks of reactions and plots of concentrations.

CoSBi Lab comprises five free, downloadable software prototypes:

  • Beta Workbench: a collection of tools explicitly designed to represent biological entities and their interactions.
  • Cyto-Sim: a stochastic simulator of biochemical processes in hierarchical compartments that can be isolated or allowed to communicate via peripheral and integral membrane proteins.
  • Kinfer: a tool for estimating rate constants of biochemical network models from concentration data measured at discrete time points.
  • Snazer: a modular tool designed to aid the processes of visualizing and manipulating reactive models and to share and interpret time-course data.
  • Redi: a reaction-diffusion simulator built to test new diffusion models and algorithms.

This work and other projects pursued at the Trento centre are based on the concept of “algorithmic systems biology.” A video on the CoSBi Web site defines the term as representing biological entities as programs.

“The interaction of two entities,” Priami explains in the video, “becomes the exchange of a message between the programs, and the simultaneous execution of the programs simulates the dynamics of a biological system.”

The collaboration between Microsoft Research Cambridge and the University of Trento has its roots in a December 2004 gathering in Trento of the inaugural Converging Sciences Conference, organized to build a new framework for collaborative scientific research in Europe.

Less than two months later, on Feb. 2, 2005, Gates signed the agreement that created the centre, along with Bassi; Letizia Moratti, minister of Education, University, and Research; Lucio Stanca, minister of Innovation and Technology; and Gianluca Salvatori, councilor of Planning, Research, and Innovation for the province of Trento.

The agreement stipulated that all research results and prototypes would be made available to the international research community for scientific pursuits.

Priami heads the centre’s organizational structure, and the board of directors includes four members, two from the University of Trento and two from Microsoft Research. By statute, Priami is one of the university’s two board members, and he is joined by professor Pierpaolo Degano. Herbert represents Microsoft Research and is joined by Luca Cardelli, principal researcher at Microsoft Research Cambridge. Elisabetta Nones of the university acts as administrative manager.

On June 9, 2005, a Research Project Agreement was signed by Bassi and Stephen Emmott, then director of the External Research Office at Microsoft Research Cambridge and now head of Computational Science at the Cambridge lab. CoSBi was inaugurated on Dec. 7 of that year, complete with a message of well wishes from then-Italian President Carlo Azeglio Ciampi. Scientific activities began the following April.

Now, the centre includes 25 research personnel, an international, multidisciplinary—computer science, physics, chemistry, mathematics, theoretical biology, electronic engineering—assemblage that includes three senior researchers, three researchers, nine junior researchers, seven Ph.D. students, and three developers.

Their combined output has been prodigious:

  • 74 technical reports.
  • 176 published papers.
  • 8 software prototypes.
  • 149 invited talks.
  • 122 seminars organized.
  • 7 scientific events.
  • 96 visiting professors—representing 11 countries.

The centre’s work is complemented by the efforts of several collaborative partners, including the Salk Institute for Biological Studies, GlaxoSmithKline, the Centre for Integrative Biology at the University of Trento, and Magna Græcia University of Catanzaro, Italy.

The work being performed at the CoSBi facility has the potential to have wide-ranging impact. In addition to better understanding of biological systems that could enhance the use of targeted medicines to fight prominent illnesses, systems-biology research on nutrigenomics promises insights into how food can interact with DNA to activate genes that prevent the onset of diseases. And the study of webs of interaction enables the modeling and analysis of ecosystems to determine how the food chain is influenced by human-caused environmental change.

“The work conducted at the centre demonstrates the true potential of interdisciplinary research,” Cardelli said. “This is not just to transfer knowledge or techniques from one area to another, but to use the underlying culture of two disciplines to come up with new approaches and solutions that neither discipline would have imagined. This cannot be achieved by merging research groups: People have to grow into it.”