School on Physics Applications in Biology

Start time: January 11, 2016

Ends on: January 29, 2016

Location: São Paulo, Brazil

Venue: IFT-UNESP

Organizers:

• Marcus Aguiar (UNICAMP, Brazil)
• Nathan Berkovits (ICTP-SAIFR /  IFT-UNESP, Brazil)
• Roberto Kraenkel (IFT-UNESP, Brazil)
• Gabriel Mindlin (Universidad de Buenos Aires, Argentina)

Minicourse Lecturers:

• Vijay Balasubramanian (University of Pennsylvania, USA): The Maps Inside Your Head — Diversity and Self-Organization of Neural Circuits
• William Bialek (Princeton University, USA): Precision and emergence in the physics of biological systems
• Eberhard Bodenschatz (Max Planck Institute – Göttingen, Germany): Pattern Formation in Biological Systems – from oscillations to spiral waves
• Ulf Dieckmann (International Institute for Applied Systems Analysis – IIASA, Austria): Complex Adaptive Systems at the Interface of Ecology and Evolution – Modeling Adaptation, Speciation and Biodiversity Dynamics
• Stanislas Leibler (IAS Princeton/Rockfeller University, USA): Microbial Population Dynamics
• Gabriel Mindlin (Universidad de Buenos Aires, Argentina): Nonlinear dynamics and biomechanics
• Jorge M. Pacheco (U. Minho, Portugal): The evolutionary dynamics of hematopoiesis in health and disease
• Francisco C. Santos (Universidade de Lisboa, Portugal): Cooperation and the Evolution of Collective Action 
• Gustavo Stolovitzky (IBM Research and Icahn School of Medicine, USA): Introduction to Systems Biology of Cancer

Seminar Speakers:

• Silvina P. Dawson (Universidad de Buenos Aires, Argentina): Fluctuations and transport in cells and the information that can be extracted from optical experiments
• Celso Grebogi (Aberdeen University, UK): Compressive sensing based prediction of social and metabolic complex networks
• Flávia Maria Darcie Marquitti (IFGW – Unicamp, Brazil): Strategies in nature: using game theory to deal with different problems
• José N. Onuchic (Rice University, USA): From structure to function: the convergence of structure based models and co-evolutionary information
• Andre A. de Thomaz (IFGW -Unicamp, Brazil): Multimodal photonic platform to understand biological processes

Description:

Although 
new
 experimental 
technology 
is 
partly 
responsible 
for 
the
 current
 revolution 
in 
biological 
research,
 theoretical
 models
 developed
 by 

physicists 
are 
also 
playing
 an 
important
 role 
in 
changing
 the 
way 
biological 
research 
is 
being 
performed. The
 number
 of 
theoretical 
physicists 
migrating 
into 
biology
 has dramatically 
increased
 throughout 
the 
world,
 but 
South 
America 
still lags 
behind.

The three-week school on Physics Application in Biology will feature lectures by physicists who have made important contributions to different areas of biological research. This activity will include minicourses, seminars, discussion sessions and group projects on topics including neuroscience, evolutionary dynamics, biophysics, collective behavior, pattern formation and optimization. The school is intended for graduate students and postdoctoral researchers in the physical and biological sciences. There is no registration fee and limited funds are available for travel and local expenses.

This activity will be preceded by the ‘V Southern-Summer School on Mathematical Biology’. Candidates may apply either for one or both schools.

On January 20th at 15:00 there will be a Roundtable on Physics-Biology Interactions in South America.

Announcement

Satisfaction Survey:

• Click here

Photos:

• Photos of school

School Program: PDF version updated on January 24

 Click on the title of the lectures/seminars to watch the videos

*Prof. Leibler preferred not to have his lectures recorded.

Lectures Summary:

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Vijay Balasubramanian (University of Pennsylvania, USA): The Maps Inside Your Head — Diversity and Self-Organization of Neural Circuits
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How do our brains make sense of a complex and unpredictable world? In this series of lectures, I will discuss a physicist’s approach to the neural topography of information processing in the brain. First I will review the brain’s architecture, and how neural circuits map out the sensory and cognitive worlds. Then I will describe how highly complex sensory and cognitive tasks are carried out by the cooperative action of a great many specialized neurons and circuits, each of which has a simple function.   I will describe approaches towards a predictive theory of this diversity and its self-organization.  The examples will come from  circuits and systems at multiple scales in the brain that enable the senses of sight, sound, smell and place.

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William Bialek (Princeton University, USA): Precision and emergence in the physics of biological systems
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Life is more than the sum of its parts:  many of the most striking phenomena, from the spectacular aerial displays of flocking birds down to the beautiful choreography of cell movements in a developing embryo, emerge from interactions among hundreds if not thousands or even millions of components.  Perhaps less obvious is that life’s mechanisms can achieve extraordinary precision:  our visual system can count single photons, we can hear sounds that cause our eardrum to vibrate by the diameter of an atom, neurons can transmit information at rates close to the limit set by the entropy of their responses.  These lectures will explore the themes of precision and emergence as they play out in a wide range of biological systems. Central to the discussion will be the struggle to find the right balance between searching for general theoretical principles and engaging with the myriad details of experiments on particular systems.  I hope to convey the beauty of the phenomena, and the excitement that many of us feel about the opportunities for deeper theoretical discoveries.

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Eberhard Bodenschatz (Max Planck Institute – Göttingen, Germany): Pattern Formation in Biological Systems – from oscillations to spiral waves
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In my lectures I shall introduce concepts of pattern formation with special emphasis on instabilities (Turing, Reaction Diffusion, Rayleigh Benard,etc), normal form or amplitude equations, dislocation dynamics in pattern-forming systems, autonomous oscillations and  the discussion of spiral wave dynamics.

Please find some very complimentary lecture notes by Prof. Ehud Meron here in this link: http://in.bgu.ac.il/en/bidr/SIDEER/DSEEP/Ehud_Meron/Pages/reading.aspx
Please look at lecture 1-4

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Ulf Dieckmann (IIASA, Austria): Complex Adaptive Systems at the Interface of Ecology and Evolution – Modeling Adaptation, Speciation and Biodiversity Dynamics
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Understanding complex adaptive systems requires a marriage of population dynamics with adaptive dynamics. Adaptation in living systems cannot be understood without accounting for the rich embedding of populations. Conversely, predicting the future of populations, especially when exposed to strong anthropogenic impacts, requires accounting for the prospect of rapid adaptation. Providing a modern extension of classical evolutionary game theory, the theory of adaptive dynamics allows deriving the dynamic fitness landscapes governing adaptive evolution from the underlying ecological processes. This facilitates analyzing adaptation in quantitative traits under natural conditions, accounting for arbitrary forms of population structure and density regulation. Adaptive dynamics theory highlights the importance of non-optimizing evolution and contributes to understanding surprising evolutionary phenomena such as evolutionary branching, evolutionary slowing down, evolutionary suicide, and evolutionary cycling. This, in turn, enables innovative insights into life-history evolution, niche construction, and speciation, underscoring the need for integrative treatments of ecological and evolutionary dynamics. In particular, speciation is adaptive when it allows a population to escape from being trapped at a fitness minimum. That such trapping can occur – and that populations can indeed evolutionarily converge to such traps – is a counterintuitive consequence of the dynamics of fitness landscapes. For sexually reproducing species, the adaptive escape from a fitness minimum requires, and promotes, the evolution of reproductive isolation. These lectures will provide an overview of different modeling approaches linking ecological and evolutionary dynamics, ranging from evolutionary games, adaptive dynamics theory, and evolutionary reaction-diffusion systems to agent-based eco-genetic models tackling the complexities arising from the genetic, spatial, and demographic structure of real-world systems.

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Dieckmann U & Ferrière R (2004). Adaptive dynamics and evolving biodiversity. In: Evolutionary Conservation Biology, eds. Ferrière R, Dieckmann U & Couvet D, pp. 188–224. Cambridge University Press. http://www.iiasa.ac.at/~dieckman/reprints/DieckmannFerriere2004.pdf

Meszéna G, Kisdi É, Dieckmann U, Geritz SAH & Metz JAJ (2001). Evolutionary optimisation models and matrix games in the unified perspective of adaptive dynamics. Selection 2: 193–210. http://www.iiasa.ac.at/~dieckman/reprints/MeszenaEtal2001.pdf

Dieckmann U & Doebeli M (1999). On the origin of species by sympatric speciation. Nature 400: 354–357. http://www.iiasa.ac.at/~dieckman/reprints/DieckmannDoebeli1999.pdf

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Stanislas Leibler (IAS Princeton/Rockfeller University, USA): Microbial Population Dynamics
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I will describe recent experiments on: 1) behavior of individual microbes, and its non-trivial inheritance; 2) population dynamics of microbial ecosystems; 3) some general theoretical issues connected with the fitness value of information, the evolution of inheritance systems and the dimensional reduction observed in biological systems.

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Gabriel Mindlin (Universidad de Buenos Aires, Argentina): Nonlinear dynamics and biomechanics
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Behavior emerges as a the result of a complex interplay between the nervous system and a set of bio-mechanical devices used to interact with the environment. These devices are in general nonlinear, and therefore capable of displaying complex dynamics even when subjected to simple instructions from the nervous system. In these lectures we’ ll explore the rich variety of behaviors that can emerge when the richness of nonlinear dynamics is at the disposal of the nervous system.

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Jorge M. Pacheco (U. Minho, Portugal): The evolutionary dynamics of hematopoiesis in health and disease

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In this series of lectures, I will review a unified mathematical model of hematopoiesis that I have helped developing over the last decade. This will allow me to introduce a simple model which is able to describe hematopoiesis in healthy as well as in a sick individuals, with particular emphasis placed on blood cancers. The model is intrinsically stochastic, but given the staggering number of blood cells that entail hematopoiesis, continuous limits will also be used at profit. Originating in allometric data on terrestrial mammals, I will also have a chance to establish the connection with blood cancers that happen in other mammals, at the same time answering fundamental questions such as: Are mice good model systems of humans ? At last, I will show how extensions of the model allow us to view cancer as an evolutionary game between competing species with conflicting strategies.

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Francisco C. Santos (Universidade de Lisboa, Portugal): Cooperation and the Evolution of Collective Action
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The emergence and sustainability of cooperation, traversing areas as diverse as Ecology, Economics, Political Science or Psychology, is perhaps one the most paradigmatic open questions in complex systems and interdisciplinary research. Cooperation dilemmas occur at all scales and levels of complexity, from cells to global governance. In all cases the tragedy of the commons threatens the possibility of reaching the optimal solution associated with global cooperation. By combining game theory, stochastic population dynamics, and network science, I shall start by analyzing key aspects at the foundations of collective action from reciprocity, and reputations, to signaling, and the role played by the intricate nature of modern social networks. I will then move to more complex scenarios of public goods and N-person games, discussing in which way risk, uncertainty, small-scale agreements, sanctioning institutions or wealth inequality may influence cooperation at a global scale.

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Gustavo Stolovitzky (IBM Research and Icahn School of Medicine, USA): Introduction to systems biology of cancer
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Cells are fascinating systems to study from the perspective of dynamics, complexity and resilience. The study of cells in their cancer state adds to that fascination the urgency of dealing with a malignancy that is the second killer in the world, accounting for 1 out of every 4 deaths in the US only. The advent of fast and cheap sequencing technologies in the last decade brought with it the ability to probe cancer at the molecular level, giving researchers the opportunity to mechanistically explore carcinogenesis, tumor progression and tumor heterogeneity. Systems biology also blossomed during the last decade and a half, bringing a healthy dose of quantitation to the study of biology by leveraging contributions of diverse disciplines such as physics, mathematics, computer science and engineering. Systems Biology deals with the biological reality by embracing its complexity and looking at all the experimentally accessible components from where it formulates models and refutable predictions. The application of systems biology to cancer is pushing the boundaries in cancer research, by enabling cancer biologists and clinicians to develop better diagnosis, prognosis and treatments tools. In these lectures I will review the most important topics in the evolving field of cancer systems biology, highlighting open-ended areas where there are interesting opportunities for new discoveries.

Seminar Abstracts:

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Silvina P. Dawson (Universidad de Buenos Aires, Argentina): Fluctuations and transport in cells and the information that can be extracted from optical experiments
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Cells are permanently interacting with their environment. This interaction usually involves the binding of molecules to receptors that are located on the plasma membrane inducing changes in a series of intracellular components that eventually generate an end response. Both the arrival of the external molecules and the cascade of events that the initial binding induces involve the transport of substances. Most often this transport includes the diffusion of relevant species that, on their way, also interact with various cell components. All these processes occur in a very fluctuating realm. Fluctuations set limits to the accuracy with which endogenous processes can occur. The physical principles that rule these limits also affect the experimental quantification of biophysical parameters in situ. The characterization of fluctuations, on the other hand, provides a way to quantify biophysical parameters. In this talk I will discuss the behavior of transport and fluctuations in cells and how the latter can be used to quantify certain parameters. To this end I will consider a simple system of reacting and diffusing species. I will introduce the idea of effective diffusion coefficients and will analyze what information is provided in such a case by optical experiments that are currently used to quantified concentrations and transport rates. I will finally discuss how these ideas can be extended to understand the time it takes for endogenous mechanisms to “read” concentration changes.

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Celso Grebogi (Aberdeen University, UK): Compressive sensing based prediction of social and metabolic complex networks
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In the fields of complex dynamics and complex networks, the reverse engineering, systems identification, or inverse problem is generally regarded as hard and extremely challenging mathematically as complex dynamical systems and networks consists of a large number of interacting units. However, our ideas based on compressive sensing, in combination with innovative approaches, generates a new paradigm that offers the possibility to address the fundamental inverse problem in complex dynamics and networks. In particular, in this talk, I will argue that evolutionary games model a common type of interactions in a variety of complex, networked, natural systems and social systems. Given such a system, uncovering the interacting structure of the underlying network is key to understanding its collective dynamics. Based on compressive sensing, we develop an efficient approach to reconstructing complex networks under game-based interactions from small amounts of data. The method is validated by using a variety of model networks and by conducting an actual experiment to reconstruct a social network. While most existing methods in this area assume oscillator networks that generate continuous-time data, our work successfully demonstrates that the extremely challenging problem of reverse engineering of complex networks can also be addressed even when the underlying dynamical processes are governed by realistic, evolutionary-game type of interactions in discrete time. I will also touch on the issue of detecting hidden nodes, on how to ascertain its existence and its location in the network, this being highly relevant to metabolic networks.

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Network reconstruction based on evolutionary-game data via compressive sensing, W.-X. Wang, Y.-C. Lai, C. Grebogi, and J. Ye, Phys. Rev. X 1, 021021 (2011)

Predicting catastrophe in nonlinear dynamical systems by compressive sensing, W.-X. Wang, R. Yang, Y.-C. Lai, V. Kovanis, and C. Grebogi, Phys. Rev. Lett. 106, 154101 (2011)

Forecasting the future: Is it possible for adiabatically time-varying nonlinear dynamical systems? R. Yang, Y.-C. Lai, and C. Grebogi, Chaos 22, 033119 (2012)

Optimizing controllability of complex networks by minimum structural perturbations, W.-X. Wang, X. Ni, Y.-C. Lai, and C. Grebogi, Phys. Rev. E 85, 026115 (2012)

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Flávia M. D. Marquitti (IFGW – Unicamp, Brazil): Strategies in nature: using game theory to deal with different problems
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Individuals of many species present different strategies when interacting with other individuals. In mutualistic interactions, for instance, individuals of different species exploit each other, resulting in net benefits for both of them. However, sometimes one of the partners can present a strategy of overexploitation of the partner. In pollination, one of the most known forms of mutualisms, nectar robbers and nectar thieves act as cheaters of plant-pollination interactions, exploring floral resources such as pollen and nectar without pollinating the flowers. Mimicry is another strategy in which some preys cheat the predators displaying a fake dangerousness to them. Males of some lizard species have different strategies to attract females for reproduction, such as territorialist males, female-like males and sneaker males. All these strategies are characterized by costs and benefits associated with the interaction between partners. The interplay between the benefits and costs of the interactions may help us understand how different strategies can coexist and how a disadvantageous strategy can become predominant in a population. We used game theory as an unifying approach to deal with these different problems.

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José N. Onuchic (Rice University, USA): From structure to function: the convergence of structure based models and co-evolutionary information
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Understanding protein folding and function is one of the most important problems in biological research. Energy landscape theory and the folding funnel concept have provided a framework to investigate the mechanisms associated to these processes. Since protein energy landscapes are in most cases minimally frustrated, structure based models (SMBs) have successfully determined the geometrical features associated with folding and functional transitions. Structural information, however, is limited with respect to different functional configurations. This is a major limitation for SBMs. Alternatively statistical methods to study amino acid co-evolution provide information on residue–residue interactions useful for the study of structure and function. Here, we show how the combination of these two methods gives rise to a novel way to investigate the mechanisms associated with folding and function.

We will also show how this combined approach can be used to develop a procedure to predict the association of protein structures into homodimers. Coevolutionary contacts extracted from Direct Coupling Analysis (DCA) in combination with SBMs guide the simulations of dimerization. Identification of dimerization contacts using DCA is more challenging than intradomain contacts since direct couplings are mixed with monomeric contacts. Therefore a systematic way to extract dimerization signals has been elusive. We provide evidence that the prediction of homodimeric complexes is possible with high accuracy. The mean RMSD is 1.38 Å for the most accurate conformations of 11 structurally diverse dimeric complexes. This methodology is also able to identify distinct dimerization conformations as for the case of the family of response regulators, which dimerize upon activation.

* Supported by the NSF

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Andre A. de Thomaz (IFGW -Unicamp, Brazil): Multimodal photonic platform to understand biological processes
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The scientific community believes there is a great chance that the next technological revolution is coming from the control of biological processes. This revolution can change many aspects of our actual life, like the way we produce food and how we fight diseases. It is clear to our group that these changes will come only from the understanding of biology at its most basic unity: the cell. Moreover, only after we understand and control the chemical reactions inside the cell it will be possible to achieve these predictions. We believe that a multimodal photonic platform is the best tool to study biological processes because of its ability to follow processes in real time without any damage to the cells.   The techniques present in this platform are: 1 or 2 photon excited fluorescence, second or third harmonic generation, optical tweezers, fluorescence lifetime imaging (FLIM) and Forster resonance energy transfer (FRET). In this seminar I will show how to assemble this integrated platform and its versatility with results from different fields of biology.

Additional Information:

List of Confirmed Participants: Updated on Dec 29

Registration: ALL participants should register. The registration will be on January 11 at the institute from 9:00 to 10:00 am. You can find arrival instruction at http://www.ictp-saifr.org/?page_id=195 Participants who have attended the previous school do not need to register again.

BOARDING PASS: All participants, whose travel has been provided or will be reimbursed by the institute, should bring the boarding pass upon registration, and collect an envelope to send the return boarding pass to the institute.

Accommodation: Participants whose accommodation has been provided by the institute will stay at The Universe Flat. Each participant, whose accommodation has been provided by the institute, has received the accommodation details individually by email.

Emergency number: 9 8233 8671 (from São Paulo city); +55 11 9 8233 8671 (from abroad), 11 9 8233 8671 (from outside São Paulo).

Ground transportation instructions: 

Ground transportation from Guarulhos Airport to The Universe Flat

Ground transportation from Congonhas Airport to the Universe Flat

Ground transportation from The Universe Flat to the institute