Last March 15th, two Master Thesis dissertations from the GCSC-UPV group:

Control of constrained biosystems.

Author: Ana Revert

Supervisor: Prof. Jesús Andrés Picó Marco.

Abstract

Biological systems (biosystems), due to their complexity and multidisplinary character, are becoming one of the challenging research topics in the field of systems and control. In this work, several tools for dealing with control subject to constraints in the area of biosystems have been explored.

Coordination of dynamical systems:
A sliding mode reference conditioning approach.

Author: Alejandr  Vignoni

Supervisor: Prof. Jesús Andrés Picó Marco.

Abstract

This work proposes a novel methodology for coordination of dynamical systems. The scheme is based on the sliding mode reference conditioning technique in two main configurations: a sort of global supervisory level in one hand, and a network of local interactions in the other.

Last March 15th, Francisco Llaneras presented his PhD Thesis dissertation:

Interval and Possibilistic Methods for Constraint-Based Metabolic Models.

Supervisor: Prof. Jesús Andrés Picó Marco.

Abstract

This thesis is devoted to the study and application of constraint-based metabolic models. The objective was to find simple ways to handle the difficulties that arise in practice due to uncertainty (knowledge is incomplete, there is a lack of measurable variables, and those available are imprecise). With this purpose, tools have been developed to model, analyse, estimate and predict the metabolic behaviour of cells.

The document is structured in three parts. First, related literature is revised and summarised. This results in a unified perspective of several methodologies that use constraint-based representations of the cell metabolism. Three outstanding methods are discussed in detail, network-based pathways analysis (NPA), metabolic flux analysis (MFA), and flux balance analysis (FBA). Four types of metabolic pathways are also compared to clarify the subtle differences among them.

The second part is devoted to interval methods for constraint-based models. The first contribution is an interval approach to traditional MFA, particularly useful to estimate the metabolic fluxes under data scarcity (FS-MFA). These estimates provide insight on the internal state of cells, which determines the behaviour they exhibit at given conditions. The second contribution is a procedure for monitoring the metabolic fluxes during a cultivation process that uses FS-MFA to handle uncertainty.

The third part of the document addresses the use of possibility theory. The main contribution is a possibilistic framework to (a) evaluate model and measurements consistency, and (b) perform flux estimations (Poss-MFA). It combines flexibility on the assumptions and computational efficiency. Poss-MFA is also applied to monitoring fluxes and metabolite concentrations during a cultivation, information of great use for fault-detection and control of industrial processes. Afterwards, the FBA problem is addressed. A possibilistic approach is derived to get predictions under the assumption that cells have evolved to be optimal (Poss-FBA). It captures alternate optima and grades sub-optimality, thus relaxing the original assumption. The last contribution is a procedure to validate constraint-based models when data are scarce. This procedure mitigates validation problems with small metabolic networks.

This thesis highlights the importance of accounting for uncertainty when modelling living cells and promotes a constraint-based perspective: if we cannot exactly model how cells operate, use the knowledge available to distinguish what is possible from what is not. Following this idea, methods are proposed that start by representing the available knowledge and its uncertainty, and then exploit this representation to generate reliable new information.

In the following site the reader will find updated information regarding this thesis.
This includes corrections and clarifications, connections with future works, publications,
software and tools, etc.

http://science.ensilicio.com/Thesis

Participating in the Biocomplexity XI Workshop: The evolution of cooperation.

Dec. 3rd-Dec. 5th, 2010

Bloomington, IN, USA

Cooperation occurs throughout the biological world, and similar
mechanisms and patterns of cooperative organization appear across the
hierarchies of biological structures:

Genes organize into genomes, cells into multicellular organisms,
organisms into institutions and societies, and species into ecologies.
Might there be important analogies between mechanisms at one such level
of organization and mechanisms at a different level?

Cooperation benefits a society, while evolution selects at the level
of individuals. Despite insights into the mathematics of selection in
the presence of cooperation, many aspects of the development of
cooperation remain mysterious in practice.

What is an individual? Is individuality discrete or continuous?
Can selection act simultaneously on multiple scales? How did cells
abandon reproduction to a specialized germ line? How did stable
multicellularity evolve in the face of noncooperative advantages?

When does stable cooperation require enforcement? Can the fitness
functions of evolutionary theory capture an individual’s transfer of
fitness to a collective? Are individuals the correct fundamental units
of cooperative systems?

The intra-cellular cooperation of genes, molecular machines, and
organelles resembles a microscopic city; does the heterogeneity of the
conventional units of biology reflect an ancient cooperation predating
the origin of life?

Is an ecosystem composed of individuals, or is an individual
composed of ecosystems? Can the evolution of cooperation inform
engineering or economic regulation?

This workshop will investigate these subtle and provocative issues,
which are often ignored or misunderstood.

Talks will cover subjects ranging from cooperation inside of cells,
bacterial biofilms, social insect colonies, human institutions and
societies, cancer etiology and progression to the question of how single
cells subsumed their fitness in favor of multi-cellular collectives.
 

Biocontrol member Alejandro Vignoni, participates in the IGEM Valencia 2010 Team, at the IGEM competition, in MIT, Cambridge, MA from 5-8 Dec 2010.

The International Genetically Engineered Machine competition (iGEM) is the premiere undergraduate Synthetic Biology competition. Student teams are given a kit of biological parts at the beginning of the summer from the Registry of Standard Biological Parts. Working at their own schools over the summer, they use these parts and new parts of their own design to build biological systems and operate them in living cells. This project design and

competition format is an exceptionally motivating and effective teaching method.

Photo Gallery of IGEM Valencia Team 2010