Workshop Metabolism and mathematical models: Two for a tango – 5th Edition
Ronan M.T. Fleming
Title: Workshop Metabolism and mathematical models: Two for a tango – 5th Edition
Dates: November 20-21, 2025
Location: This workshop will be held in a virtual way.
The topic of this workshop is metabolism in general. Besides an exploration of the biological, biochemical and biomedical aspects, the workshop will also aim at presenting some of the mathematical modelling, algorithmic theory and software development that have become crucial to explore such aspects.
The workshop is open to the whole community in general.
Keynote lecturers
Kai Blin, Novo Nordisk Foundation Center for Biosustainability, Denmark
Title talk: To ML or not to ML – Thoughts about Limitations and Trade-Offs after 15 Years in Genome Mining
Short abstract: Researchers panning on building predictive tools are faced with a decision on which computational approach to use. Should they build an expert system that carefully pre-encodes all available domain knowledge in an inference engine? Should they deploy some sort of Machine Learning or Artificial Intelligence approaches instead? This talk will present the trade-offs of this decision, talk about the limitation of both expert and ML systems, and illustrate these in the field of mining microbial genomes for gene clusters encoding interesting biosynthesis pathways.
Tobias Engl, Max Planck Institute for Chemical Ecology, Germany
Title talk: Who am I and how many? Molecular and metabolic integration of multiple symbionts
Short abstract: The evolutionary success of insects is to a large extend due to their frequent symbioses with often obligate, intracellular microorganisms. These contribute metabolic capabilities which were otherwise never acquired by animals such as the synthesis of essential nutrients, but require host provision of basic nutrient. Such a meta-organism must balance the costs and benefits that arise from these intimate relationships to maximize overall fitness. This selection pressure can lead to the rise of various mechanisms of integration of symbiotic partners into the host biology. I will present ongoing research on three levels of regulation and integration: the cell number of a single (species of) symbiont, the metabolic contribution of two symbiont species and the incorporation of three complementary symbiont strains.
Ronan Fleming, University of Galway, Ireland
Title talk: Variational kinetics: a variational formulation of reaction kinetics
Short abstract: Established genome-scale modelling methods primarily predict reaction fluxes, whereas established high-throughput experimental technologies primarily measure molecular-species concentrations. This apparently paradoxical situation has arisen because implementing the nonlinear constraints that represent reaction-kinetic rate equations is challenging without resorting to convenient yet inaccurate approximations. We present a mathematically and computationally tractable solution to this problem. First, we introduce a mathematical reformulation of established knowledge of metabolic reactions and reaction kinetics in matrix–vector notation. We then present variational kinetics, a novel approach that satisfies steady-state reaction kinetics at genome scale using new mathematical and numerical optimisation techniques. Finally, we illustrate how this approach can efficiently optimise over the set of steady-state reaction fluxes, thermodynamically feasible kinetic parameters, and kinetically feasible elementary or macroscopic rate laws.
Alicia J. Kowaltowski, University of São Paulo, Brazil
Title talk: How Mitochondria Respond to Changes in Caloric Intake
Short abstract: In humans, obesity is associated with increased incidence of a variety of age-related diseases. Similarly, laboratory rodent lifespans are limited by obesity, including overeating promoted by ad libitum access to standard chow diets. Indeed, a daily limitation of caloric intake (calorie restriction) has been widely shown to enhance lifespans and prevent age-related diseases in rodents. We will discuss the metabolic effects of caloric restriction, and show that mitochondrial bioenergetics and calcium homeostasis are regulated by caloric restriction, with an impact on tissue stress responses.
Alejandra Pietro Davó, National Autonomous University of Mexico, Mexico
Title talk: Microbiome metabolisms from underground anchialine cave sediments and the sponges that dwell in them
Short abstract: The Yucatan peninsula is characterized by the karstic composition of its soils and the resulting underground caves and conduits which encompass the largest underground river in the world. In this river, the microbial communities and their metabolisms sustain the ecosystem that would otherwise be deprived of energy inputs. Furthermore, the coastal areas of the river can be influenced by tides, stratifying the water column and making methanotrophy and chemoautotrophy especially important. Recently, our lab has studied the differences in microbial sediment bacteria from coastal and inland cenotes and their potential for natural product discovery. In one of these coastal caves, we discovered sponges with microbiomes showing important roles in biogeochemical cycles, including sulfur, nitrogen and methane. These results suggest that sponges can act as biofermenters, maintaining the health of the coastal mangrove ecosystem established above the caves they inhabit.
Jean-Marc Schwartz, University of Manchester, UK
Title talk: Can we predict the metabolic objectives of a cell?
Short abstract: Constraint-based modelling approaches such as flux balance analysis (FBA) enable testable predictions of metabolic behaviour from genome-scale metabolic models (GEMs). However, traditional FBA assumes organisms optimise a single metabolic objective, typically biomass maximisation, which is not universally valid. Complex, phase-dependent systems like Chinese Hamster Ovary (CHO) cells exhibit distinct metabolic priorities across bioproduction phases, complicating the selection of objective functions for accurate flux predictions. To address this, we implement a novel algorithmic approach using simulated annealing to minimise a discrete mismatch function that quantifies deviation between model predictions and experimental qualitative trends. This method successfully identifies phase-specific multilinear objective functions matching experimental flux findings, revealing objective functions that provide insight into time-dependent metabolic priorities. These results emphasise the need for context-specific metabolic objectives in FBA models of mammalian cells and propose a translatable optimisation framework for their discovery. This approach not only enhances CHO cell modelling for bioprocess optimisation but also contributes broadly to reducing uncertainty in metabolic network analyses across various organisms.
Discussions on open questionsFor this fifth edition of the workshop, besides the keynote talks, there will be also two slots, one per day, for a discussion on two specific open questions:
- Discussion 1: Objective functions are essential components of genome-scale models. Among the most complex and useful objective functions is the so-called “Biomass Function” which allows to represent cell proliferation. For the model to be accurate, this function must represent as precisely as possible the composition of the cells being modelled. This requires intensive experimental datasets, which in many cases are not available. As a consequence, very often, biomass functions are borrowed from other existing models, sometimes based on very different cells. This results in chains of artefactual descriptions and model failures in representing reality. How then to improve the objective functions? Is it worth to create repositories for them? Is it worth to implement a community effort to produce, compile, curate and make available datasets of different cellular models to produce more reliable biomass functions?
- Discussion 2: This second discussion slot will focus on the development of an ontology for genome-scale metabolic models (GEMs). The session will consider how semantic representations can enhance GEM reconstruction, enable logical consistency checks, and support the comparison of metabolic networks. Insights from a recent online survey may also be discussed. This survey, which is still ongoing, is available here.
In order to cover a larger audience, the workshop will take place in the afternoon, CET time (French time), on both days.
Thursday 20
Friday 21
14h00-14h10 CET time
Introduction to the workshop
Introduction to the second day
14h10-14h40 CET time
Talk 1: Ronan Fleming
Talk 4: Alicia J. Kowaltowski
14h40-14h55 CET time
Questions and discussion on Talk 1
Questions and discussion on Talk 4
14h55-15h05 CET time
Short break
Short break
15h05-15h35 CET time
Talk 2: Alejandra Pietro Davó
Talk 5: Jean-Marc Schwartz
15h35-15h50 CET time
Questions and discussion on Talk 2
Questions and discussion on Talk 5
15h50-16h00 CET time
Short break
Short break
16h00-16h30 CET time
Discussion 1
Discussion 2
16h30-17h00 CET time
Talk 3: Kai Blin
Talk 6: Tobias Engl
17h00-17h15 CET time
Questions and discussion on Talk 3
Questions and discussion on Talk 6
17h15-17h30 CET time
Final discussion and conclusion of the first day
Final discussion and conclusion of the workshopRegistration
Registration is free but mandatory. To register, go to this link. Registration will close on November 19 at 6pm CET time (French time). The link to the workshop will be sent to all those who registered on November 20, check your mail boxes at the address indicated when registering.
OrganisationMariana Galvão Ferrarini, Max-Planck Institute for Chemical Ecology, Jena, Germany
Sabine Peres, University of Lyon 1, CNRS, and Inria, France
Marie-France Sagot, Inria, CNRS and University of Lyon 1 UMR 5558, France
Ariel M. Silber, Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo (USP), São Paulo, Brazil
Susana Vinga, Instituto Superior Técnico and INESC-ID, Lisbon, Portugal
Information on the participants will be made available later.