March 9th
Speaker: Miguel Rocha
Affiliation: Universidade do Minho

March 16th
Speaker: Thiago Guzella
Affiliation: IGC, Quantitative Organism Biology Group

March 23th
Speaker: Filipa Alves
Affiliation: IGC, Plant Development Group

March 30th
Speaker: Vitor Sousa
Affiliation: IGC, Population and Conservation Genetics Group

PREVIOUS SEMINARS

February 23th, 2010
Speaker: Manuel Marques-Pita
Affiliation: IGC - FLAD Computational Biology Collaboratorium and Indiana University (Group leader, Prof. Luis Rocha)
Title: A Complex Systems Perspective on the Modelling of Biochemical Networks
Abstract: In this talk I will discuss the problem of understanding how the dynamics of highly interconnected biochemical networks can be harnessed to achieve control and regulation of phenotypic behaviour. I will introduce an analytical approach that treats the dynamics of robust complex networks as a collective computation problem. This approach can be best summarized as the identification of Ňdynamical motifsÓ that characterize the attractor behaviour of discrete dynamical systems, with a dramatic reduction of their state spaces. Dynamical motifs are a (epigenetic) property of the dynamics of many interacting genes and proteins, that is not observable from their individual function. I will show that dynamical motifs can allow us to understand essential aspects of the collective computation performed by gene regulation networks. I will focus specifically on the inference of control mechanisms, modularity and robustness in discrete complex networks. As an illustrative example, I will use a well-known discrete model of the fruit fly segment polarity network.

February 17th, 2010
Speaker: Danesh Tarapore
Affiliation: IGC, Quantitative Organism Biology Group
Title: Factors modulating the efficiency of division of labor in social insect societies
Abstract: If one were to ask what life forms on this planet are extremely widespread, highly social and live in very large groups, the answer would quite surprise us. It is hard to imagine that social insects (ants, social bees, social wasps and termites) where an individual measures no more than a few centimeters, would fit the bill. And yet these social insects represent a large proportion of the world's insect biomass and their net energy consumption surpasses that of vertebrates in most terrestrial habitats. One of the primary reasons cited for this resounding ecological success of social insects is the sophisticated division of labor employed in their colonies. Social insect colonies are faced with a number of tasks such as foraging for different resources, processing these resources, looking after the brood, maintaining the nest and defending the colony against predators. Division of labor entails the efficient allocation of individuals to these different tasks to meet the requirements of the colony under changing environmental conditions. Theoretical models suggest that this colony-level flexibility in responding to external changes and internal perturbation may depend on the within-colony genetic diversity, which is affected by the number of breeding individuals. However, existing models have not considered the genetic architecture underlying the propensity of workers to perform the various tasks. In this talk, I will be describing some of the experiments performed with multi-agent simulations to investigate how both within-colony genetic variability (stemming from variation in the number of matings by queens) and the number of genes influencing the stimulus (threshold) for a given task at which workers begin to perform that task jointly influence task allocation efficiency. Although the research described will address questions primary to biology, I will also attempt to abstract concepts and ideas that may prove useful in designing multi-robot systems.

February 9th, 2010
Speaker: Andreia Amaral
Title: Finding selection footprints in domesticated genomes using massive parallel sequencing
Abstract: We investigated whether selection footprints can be identified from GA (Genome analyzer) sequences generated from pooled Reduced Representation Libraries and covering approximately 2% of the genome of Large White, Landrace, Pietrain, Duroc and Wild Boar. Methods were developed to estimate Nucleotide Diversity (ND) considering that, GA sequences were obtained from pooled DNA, singletons were removed and the sequencing error rate. The average ND ranged from 0.0008 to 0.002 depending on chromosome and breed. Genomic locations that have been, putatively, under selection were identified. We found signals of positive selection on SSC8 in the region containing the KIT gene, for white breeds but not for Duroc and Wild Boar. Signals of balancing selection were found for regions on SSC7 containing genes from the MHC complex and from the olfactory receptors complex. Enrichment analysis of KEGG-pathways showed that for regions under positive selection, swine breeds showed higher enrichment of pathways related to growth whereas Wild Boar showed higher enrichment of pathways related to immunity and robustness. Balancing selection resulted in the significant enrichment of pathways related to the olfactory receptors activities in all swine breeds and Wild Boar. Our results raise the possibility of using GA sequencing of pools for identification of selection footprints and present the first global map of regions under selection in the swine genome.

February 2nd, 2010
Speaker: Jorge Sousa
Title: EpiAL - An Epigenetic Approach for an Artificial Life Platform
Abstract: The biological knowledge regarding how living systems work has advanced significantly during the past years. The Neo-Darwinist evolutionary theory is nowadays not soundisputed as it has been, mostly due to an increased effort in uncovering the relations between the environment and the regulation and development of organisms. A new, broad area, Evo-Devo, incorporates the study of development and regulation into evolutionary, population and ecological frameworks. Epigenetics, a relevant part of this new field, focus on the study of genetic mechanisms that produce phenotypic variation without changes in the base nucleotides. It also studies eventual inheritance processes of such acquired variations. Generally under the influence of the classical paradigms, Artificial Life models scarcely tackle these new ideas, focusing on classical evolutionary models and mechanisms. We propose an epigenetic based Artificial Life model - EpiAL - that considers regulatory agents and environmental dynamic conditions that influence the genetic expression of such agents. The model is able to simulate the evolution of virtual organisms that possess epigenetic regulatory and inheritance mechanisms, thus allowing the study of the evolutionary processes and the transmission of specific traits under dynamic environments. In our model, notorious differences were observed in the evolutionary behavior of populations, regarding the epigenetic variables and variants. Although an abstract and minimal model, the behavior observed with the performed experimentations could be a hint that there is space in Artificial Life for the inclusion of these new ideas and theories, namely on developmental and epigenetic issues, and that Artificial Life models could, in fact, be of use in the study of these new dynamics and complex processes in development and evolution.

January 19th, 2010
Speaker: Ricardo Aguas
Affiliation: IGC, Collective Dynamics Group
Title: The versatility of mathematical models
Abstract: Simple mathematical models can help make sense of observed epidemiological phenomena, by raising or analyzing hypothesis with biological relevance, and by allowing the estimation of a reasonable number of parameters which are crucial to the transmission dynamics . More complex models are usually over parameterized, requiring extensive knowledge of the biological processes at hand to ensure the significance and accuracy of the results. Simple models allow for a relatively easy exploration of both the parameter space and model topology. This enables the identification of interesting dynamical behaviors for a given combination of parameters and model structure, which can then be used as a reference when constructing more complicated models. Simple models can then serve as stepping stones towards more accurate and detailed models, which can be used to realistically simulate the intricacies of public health interventions, especially when dealing with elimination scenarios, as we have done in Chapters 4 and 5. Simple models can thus be used as ŇnullÓ models against which we can compare more complex frameworks, inferring how the added levels of complexity improve the modelŐs agreement with the observed variable of interest, or change the qualitative behavior of the system at hand.

January 12th, 2010
Speaker: Carlos Tamulonis
Affiliation: Section for Computational Science, Universiteit van Amsterdam, NL
Title: A Cell-based Model of Nematostella vectensis gastrulation including bottle-cell formation, invagination and zippering
Abstract: The gastrulation of Nematostella vectensis, the starlet sea anemone, is morphologically simple yet involves many conserved cell behaviors such as apical constriction, invagination, bottle-cell formation, cell migration and zippering found during gastrulation in a wide range of more morphologically complex animals. In this presentation I'll describe Nematostella gastrulation using a combination of morphometrics and computational modeling. Through this analysis, we find that gastrulation in Nematostella is a non-trivial problem, in which two distinct cell domains must change shape to match each other geometrically, while maintaining the integrity of the embryo. Using a detailed cell-based model capable of representing arbitrary cell-shapes such as bottle-cells, as well as filopodia, localized adhesion and constriction, we are able to associate emergent macroscopic changes in embryo shape to individual cell behaviors. We have developed a number of testable hypotheses based on the model. First, we hypothesize that the blastomeres need to be more contractile at their apical ends, relative to the rest of the cell perimeter, in order to be able to hold their wedge shape and the dimensions of the blastula, regardless of whether the blastula is sealed or leaky. We also postulate that bottle-cells are a consequence of cell strain and low cell-cell adhesion, and can be produced within an epithelium even without active cell shape changes. Finally, we are able to simulate gastrulation based on the conceptual model of Magie et al. (2007). We find that the our simulations are qualitatively similar to actual embryos based on morphometric data we have collected and we postulate that apical constriction, filopodia and de-epitheliazation are necessary and sufficient for gastrulation based on parameter variation studies.

January 5th, 2010
Speaker: Lounès Chikhi
Affiliation: IGC, Population and Conservation Genetics Group
Title: Back to the Neolithic: is DNA mytho-chondrial?
Abstract: There is an ongoing debate regarding the relative contributions of early farmers and hunter-gatherers during the peopling of Europe during the Neolithic transition. In the last fifteen years there has been an increasing use of genetic data, including ancient DNA, to resolve this debate. Here I will present new results on Y chromosome and mitochondrial DNA data suggesting that the contribution from the Near-East is probably large, contrary to an increasingly held view.

December 15th, 2009
Speaker: Flavio Coelho
Affiliation: IGC, Theoretical Epidemiology Group
Title: Treating uncertainty in mathematical models
Abstract: I will present the issue of uncertainty in models and discuss tools for dealing with it in both deterministic and stochastic models. Applications to various models will also be presented and discussed.

November 24th, 2009
Speaker: Jorge Carneiro
Affiliation: IGC, Quantitative Organism Biology Group
Title: Quantitative Organism Biology
Abstract: Cells of multicellular organism cooperate to ensure body development and maintenance. They do this in a collective distributed manner, without any master or plan. At the qob lab we investigate the multilevel mechanisms that give rise to whole organism properties, in search for general principles of organisation of natural systems and of the design of artificial systems. I will overview the main lines of our research programme, pinpointing past contributions to the mathematical theory of multicellular systems, and interspersing these with contributions to the development of methods for quantitative analysis of cells, cell populations, and tissues. I will also discuss the next steps of this research programme.

November 17th, 2009
Speaker: Jose Pereira Leal
Affiliation: IGC, Computational Genomics Group
Title: Cell biology (bio)informatics
Abstract: Cell Biology and Evolutionary biology are two fields of research that have developed with their backs turned to each other. It is our conviction that both can gain a lot, if evolution opens the black box of the cell, and if cell biology acknowledges that cellular structures and function are the result of evolution. We are trying to make this marriage happen, namely by developing the necessary tools and analysis frameworks. Myself and members of my lab will discuss some of our present and future work in our quest to develop an evolutionary cell biology.

November 10th, 2009
Speaker: Luis M. Rocha
Affiliation: IGC - FLAD Computational Biology Collaboratorium and Indiana University
Title: Studying the Evolutionary Rationale of RNA Editing with Agent-Based Simulations (II)

November 3rd, 2009
Speaker: Luis M. Rocha
Affiliation: IGC - FLAD Computational Biology Collaboratorium and Indiana University
Title: Studying the Evolutionary Rationale of RNA Editing with Agent-Based Simulations
Abstract: We started studying the evolutionary implications of RNA Editing with computational models in the 1990s. Our latest agent-based model of genotype editing is defined by two distinct genetic components: a coding portion encoding phenotypic solutions, and a non-coding portion used to edit the coding material. This set up leads to an indirect, stochastic genotype/phenotype mapping which captures essential aspects of RNA editing found in Nature. Previously, we have established the quantitative performance advantages of genotype editing against the canonical evolutionary algorithm in static and dynamic environments of various types. In this talk, we present a study of the qualitatively different evolutionary solutions attainable via genotype editing in drastically changing environments. In particular, we show how genotype editing can be advantageous in dynamical environments, namely with the emergence of regulatory signals and memory of previous environment---a capacity not attainable by evolutionary algorithms that use only coding genetic material.
Our research goal is twofold: (1) to study the role of RNA Editing regulation in the evolutionary process, and (2) to investigate the conditions under which genotype edition improves the optimization performance of bio-inspired evolutionary algorithms. We have shown that genotype edition allows evolving agents to perform better in several classes of fitness functions, both in static and dynamic environments. We are also investigating the ways in which the indirect genotype/phenotype mapping resulting from genotype editing leads to a better exploration/exploitation compromise in the search process.

October 27th, 2009
Speaker: Nuno Sepulveda
Affiliation: IGC, Quantitative Organism Biology Group
Title: How is the T-cell repertoire shaped?
Abstract: The answer to many fundamental questions in Immunology require the characterization of the T-cell repertoire and its dynamical properties throughout life. With the question "how the T-cell repertoire is shaped?" in mind, I summarize the work that I did during my PhD, paying special attention to the Crossregulation model that have been proposed to describe peripheral selection of the regulatory and conventional T cell repertoires. A set of predictions for the shape of these repertoires are put forward by the model, which were then tested against available experimental data through the analysis of several statistical models. Some predictions were confirmed but more definite conclusions would require large samples sizes that those currently used.

October 20th, 2009
Speaker: Alekos Athanasiadis
Title: Computational studies on the role of A to I RNA editing in gene evolution
Affiliation: IGC, Protein - Nucleic Acids Interactions Group
Abstract: Adenosine deamination by RNA specific deaminases (ADARs) is the most widespread enzymatic modification of RNA, present in all animal species. This RNA modification which alters the information content of mRNAs and non-coding RNAs is shown to be orders of magnitude more common than previously thought: it is estimated that one every 2000 bases in human primary transcripts differs from it's corresponding genomic sequence. A to I editing introduces variation in primary transcript sequences that is comparable or exceeds that of alternative splicing. In my talk I describe you our work on the identification of RNA editing targets and the use of this information in developing an in silico model of this RNA modification aiming at clarifying how this recourse of sequence variation may alter the process of gene evolution.

October 13th, 2009
Speaker: Andreas Bohn
Affiliation: ITQB, Systems Biodynamics Group
Title: Knowledge discovery and modeling in complex ecophysiological systems
Abstract: A principal challenge of the research at the Systems Biodynamics Groupis to discover knowledge in data sets obtained from the time-resolvedobservation of entire organisms under realistic environmental conditions. This means dealing with sparse data contaminated with outliers and missing data, which requires specific analysis approaches, combining quantitative and visual exploration, and urges to integrate data-derived knowledge with knowledge coming from other sources like quantitative and semi-quantitative models.In the present talk I will survey results from recent analyses of multivariate circadian rhythms in sloths and menopausic women, as well as of ecophysiological processes, e.g. biomass growth, in phototrophic biofilms. I will discuss how this work is to be integrated with modeling efforts, and how novel computational tools could improve the interdisciplinary interaction with experimental scientists. In particular the possible role of semantic concepts in knowledge integration will be highlighted. I will close by presenting an outlook on two new projects of our group in computational plant sciences, and assess how they complement the present project portfolio.

October 6th, 2009
Speaker: Claudine Chaouiya
Affiliation: IGC, Network Modelling
Title: Modelling and Analysis of Large Biological Regulatory Networks: logical and Petri net approaches
Abstract: The complexity of biological regulatory networks calls for the development of proper mathematical methods to model their structures and to obtain insights in their dynamical behaviours. One popular qualitative approach consists in modelling regulatory networks in terms of logical equations (using either Boolean or multi-valued discretisation). To cope with the increasing complexity of regulatory networks, we develop dedicated methods for their qualitative modelling and dynamical analysis. I will shortly present a series of new means for the analysis of logical models. In this context, a promising approach consists in a modular and hierarchical modelling. I will introduce our project on a Petri net based framework, which allows us to consider the composition of intra-cellular logical regulatory graphs, accounting for inter-cellular communications. This modelling approach will be challenged with two applications, namely the dorsal appendage formation in Drosophila egg on the one hand, and Th lymphocyte differentiation in the periphery, on the other hand.

]]> filipa http://eao.igc.gulbenkian.pt/seminars//archives/2009-07.html#e2009-07-06T16_00_00.txt 2009-07-06T16:00:00+00:00 2009-07-06T16:00:00+00:00 2009-07-06T16:00:00+00:00 Previous Seminars - 2009 Affiliation

Gulbenkian Doctoral Programme in Biomedicine (PGDB)

A unifying conceptual model for the physiological function of PrPC and PrP-dependent toxicity

(not supplied)

Gulbenkian Doctoral Programme in Biomedicine (PGDB)

A unifying conceptual model for the physiological function of PrPC and PrP-dependent toxicity

(not supplied)

IGC (Population and Conservation Genetics Group) and Institut National des Sciences Appliquées de Toulouse

The development of a spatial simulation tool for population genetics: early stages

Genetic data are increasingly used to study the evolution of natural populations. This has led to the development of inferential methods to reconstruct the demographic history of these populations. Most of the statistical methods used ignore structure and space and assume that populations can be regarded as panmictic. However, there is an increasing recognition that it is important to explicitly model space, either by using stable “stepping-stone” models (i.e. assuming that populations are at equilibrium) or by allowing for spatial expansions. Unfortunately there are very few tools that allow population geneticists to study the properties of genetic data under spatial expansions and admixture events. Here we present the early stages of a program that should allow doing that. The aim of this talk will be to present the program which is still at an early stage of development, and discuss some of the choices made.

IGC (Population and Conservation Genetics Group) and Institut National des Sciences Appliquées de Toulouse

The development of a spatial simulation tool for population genetics: early stages

Genetic data are increasingly used to study the evolution of natural populations. This has led to the development of inferential methods to reconstruct the demographic history of these populations. Most of the statistical methods used ignore structure and space and assume that populations can be regarded as panmictic. However, there is an increasing recognition that it is important to explicitly model space, either by using stable “stepping-stone” models (i.e. assuming that populations are at equilibrium) or by allowing for spatial expansions. Unfortunately there are very few tools that allow population geneticists to study the properties of genetic data under spatial expansions and admixture events. Here we present the early stages of a program that should allow doing that. The aim of this talk will be to present the program which is still at an early stage of development, and discuss some of the choices made.

Theoretical Evolutionary Genetics, CMAF, Lisbon University, Portugal

Genetic linkage and mutation rate instability

We propose a new hypothesis that clonal evolution is fundamentally flawed due to mutation rate instability: under strong genetic linkage, adaptation by natural selection makes this instability strongly asymmetric, thereby driving mutation rates to intolerable levels and causing the population to abruptly go extinct Đ a process that has been dubbed the "mutation-rate catastrophe".

I will describe the population-biological process, briefly outline the theory, present preliminary experimental data, and discuss potential applications, including possible implications for a new mode of action of the immune system.

Theoretical Evolutionary Genetics, CMAF, Lisbon University, Portugal

Genetic linkage and mutation rate instability

We propose a new hypothesis that clonal evolution is fundamentally flawed due to mutation rate instability: under strong genetic linkage, adaptation by natural selection makes this instability strongly asymmetric, thereby driving mutation rates to intolerable levels and causing the population to abruptly go extinct Đ a process that has been dubbed the "mutation-rate catastrophe".

I will describe the population-biological process, briefly outline the theory, present preliminary experimental data, and discuss potential applications, including possible implications for a new mode of action of the immune system.

Microsoft Research, Trento, IT

Dynamic spatial games to understand cooperation in tumor formation

Authors: Matteo Cavaliere, Tarcisio Fedrizzi, Ferenc Jordán, Sean Sedwards & Attila Csikász-Nagy

Abstract: We propose a generative model, named "dynamic spatial game" (DSG) as an extension of "spatial game" proposed by Nowak and May [1]. DSG combines graph transformations and game theory to describe the role of cell-to-cell interactions during tissue formation and cancer development. The nodes of the graph represent cells and spatial interactions in the tissue are represented by the edges. Each cell acts as a player of a "game" where it interacts with its neighbors by sharing growth factors, apoptotic or anti-apoptotic signals etc., which determine the fitness of the cell. Depending on the gained fitness the cell divides, rests in G0 or dies. In the next step the graph is updated dynamically by adding or removing nodes, simulating a 2D tissue [2]. We test the role of cooperation in tissue formation and tumor development by simulating the dynamic spatial games of normal, mutated and multi-mutated (tumor) cells, where partially transformed mutated cells cooperate by sharing resources [3]. We investigate how the mutation rate and cooperation strength influences the timing of cancer development and discuss possible further extensions of the model to understand how cell-to-cell interactions influence cancer development.

[1] M. Nowak, R.M. May, (1992) Evolutionary games and spatial chaos, Nature, 359, 826 - 829.

[2] S. Bar-Duvdevani, L. Segel, (1994) On topological simulations in developmental biology, J Theor Biol, 166, 33-50.

[3] R. Axelrod, D.E. Axelrod, K.J. Pienta, (2006) Evolution of cooperation among tumor cells, PNAS, 103, 13474-9.

Microsoft Research, Trento, IT

Dynamic spatial games to understand cooperation in tumor formation

Authors: Matteo Cavaliere, Tarcisio Fedrizzi, Ferenc Jordán, Sean Sedwards & Attila Csikász-Nagy

Abstract: We propose a generative model, named "dynamic spatial game" (DSG) as an extension of "spatial game" proposed by Nowak and May [1]. DSG combines graph transformations and game theory to describe the role of cell-to-cell interactions during tissue formation and cancer development. The nodes of the graph represent cells and spatial interactions in the tissue are represented by the edges. Each cell acts as a player of a "game" where it interacts with its neighbors by sharing growth factors, apoptotic or anti-apoptotic signals etc., which determine the fitness of the cell. Depending on the gained fitness the cell divides, rests in G0 or dies. In the next step the graph is updated dynamically by adding or removing nodes, simulating a 2D tissue [2]. We test the role of cooperation in tissue formation and tumor development by simulating the dynamic spatial games of normal, mutated and multi-mutated (tumor) cells, where partially transformed mutated cells cooperate by sharing resources [3]. We investigate how the mutation rate and cooperation strength influences the timing of cancer development and discuss possible further extensions of the model to understand how cell-to-cell interactions influence cancer development.

[1] M. Nowak, R.M. May, (1992) Evolutionary games and spatial chaos, Nature, 359, 826 - 829.

[2] S. Bar-Duvdevani, L. Segel, (1994) On topological simulations in developmental biology, J Theor Biol, 166, 33-50.

[3] R. Axelrod, D.E. Axelrod, K.J. Pienta, (2006) Evolution of cooperation among tumor cells, PNAS, 103, 13474-9.

Computational Biology Group, University of Amsterdam, NL

Simple mechanics for biological phenomena

In this presentation we will talk about two very different applications of a similar model based on elementary mechanics.

The first application is a model of filamentous gliding bacteria which are sensitive to light fields and are capable of placing themselves quite precisely within the environment based on the light conditions. By simply projecting a light field on a culture of these microorganisms within a Petri dish, the population redistributes itself to reflect the projection, effectively imprinting whatever is projected onto the dish. Using a simple physical model for the filaments and equipping them with a realistic movement strategy, we reproduce the biological phenomenon.

The second application is the early development of the sea anemone Nematostella vectensis, which has been gaining momentum as a model organism in Evo-Devo. We use the same paradigm to create a model for the cells (blastomeres), which compose the hollow, multicell embryo (the blastula). These cells perform a process, called gastrulation, which essentially transforms the embryo from a monolayer epithelium into a bilayer and which is the first major event in development following fertilization. We enumerate the processes involved in this phenomenon and, using the computational model, assess the role of each towards the final result.