Bulletin of the American Physical Society
APS March Meeting 2013
Volume 58, Number 1
Monday–Friday, March 18–22, 2013; Baltimore, Maryland
Session U47: Invited Session: Controlling Biological Networks |
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Sponsoring Units: DBIO GSNP Chair: Albert-Laszlo Barabasi, Northeastern University/Harvard Medical School Room: Hilton Baltimore Holiday Ballroom 6 |
Thursday, March 21, 2013 11:15AM - 11:51AM |
U47.00001: Hard limits on control in fluctuating systems Invited Speaker: Johan Paulson All intracellular processes involve components present in low numbers, creating spontaneous fluctuations that in turn can enslave the components present in high numbers. The mechanisms are often complex, with reaction rates that depend nonlinearly on concentrations, indirect feedback loops, and distributed delays. Most systems are also sparsely characterized, with a few steps known in detail but many important interactions not even identified. I will present exact analytical mathematical frameworks for deriving limits on behavior in such systems, for example showing how hard it is to tightly control processes that involve bursts, delays, or finite signaling rates - regardless of the nature of the downstream chemical networks. I will also discuss various ways of designing experiments to rigorously exploit conditional independences in fluctuations to infer underlying mechanisms, without having to guess the nature of feedback loops or interacting processes. [Preview Abstract] |
Thursday, March 21, 2013 11:51AM - 12:27PM |
U47.00002: Controllability and observability of biological systems Invited Speaker: Yang-Yu Liu The ultimate proof of our understanding of complex biological systems is reflected in our ability to control them. Although control theory offers mathematical tools for steering engineered systems towards a desired state, a framework to control complex biological systems is lacking. In this talk I will show that many dynamic properties of complex biological systems can be quantitatively studied, via a combination of tools from control theory, network science and statistical physics. In particular, I will focus on two dual concepts, i.e. controllability and observability, of general complex biological systems. Controllability concerns our ability to drive the system from any initial state to any final state within finite time, while observability concerns the possibility to deduce the system's internal state from observing its input-output behavior. I will show that by exploring the underlying network structure of complex biological systems one can determine the driver (or sensor) nodes that with time-dependent inputs (or measurements) will enable us to fully control (or observe) the whole system. [Preview Abstract] |
Thursday, March 21, 2013 12:27PM - 1:03PM |
U47.00003: Epigenetics and Why Biological Networks are More Controllable than Expected Invited Speaker: Adilson Motter A fundamental property of networks is that perturbations to one node can affect other nodes, potentially causing the entire system to change behavior or fail. In this talk, I will show that it is possible to exploit this same principle to control network behavior. This approach takes advantage of the nonlinear dynamics inherent to real networks, and allows bringing the system to a desired target state even when this state is not directly accessible or the linear counterpart is not controllable. Applications show that this framework permits both reprogramming a network to a desired task as well as rescuing networks from the brink of failure, which I will illustrate through various biological problems. I will also briefly review the progress our group has made over the past 5 years on related control of complex networks in non-biological domains. [Preview Abstract] |
Thursday, March 21, 2013 1:03PM - 1:39PM |
U47.00004: Control of cancer-related signal transduction networks Invited Speaker: Reka Albert Intra-cellular signaling networks are crucial to the maintenance of cellular homeostasis and for cell behavior (growth, survival, apoptosis, movement). Mutations or alterations in the expression of elements of cellular signaling networks can lead to incorrect behavioral decisions that could result in tumor development and/or the promotion of cell migration and metastasis. Thus, mitigation of the cascading effects of such dysregulations is an important control objective. My group at Penn State is collaborating with wet-bench biologists to develop and validate predictive models of various biological systems. Over the years we found that discrete dynamic modeling is very useful in molding qualitative interaction information into a predictive model. We recently demonstrated the effectiveness of network-based targeted manipulations on mitigating the disease T cell large granular lymphocyte (T-LGL) leukemia. The root of this disease is the abnormal survival of T cells which, after successfully fighting an infection, should undergo programmed cell death. We synthesized the relevant network of within-T-cell interactions from the literature, integrated it with qualitative knowledge of the dysregulated (abnormal) states of several network components, and formulated a Boolean dynamic model. The model indicated that the system possesses a steady state corresponding to the normal cell death state and a T-LGL steady state corresponding to the abnormal survival state. For each node, we evaluated the restorative manipulation consisting of maintaining the node in the state that is the opposite of its T-LGL state, e.g. knocking it out if it is overexpressed in the T-LGL state. We found that such control of any of 15 nodes led to the disappearance of the T-LGL steady state, leaving cell death as the only potential outcome from any initial condition. In four additional cases the probability of reaching the T-LGL state decreased dramatically, thus these nodes are also possible control targets. Our collaborators validated two of these predicted control mechanisms experimentally. Our work suggests that external control of a single node can be a fruitful therapeutic strategy. [Preview Abstract] |
Thursday, March 21, 2013 1:39PM - 2:15PM |
U47.00005: Controllability of Complex Systems Invited Speaker: Jean-Jacques Slotine We review recent work on controllability of complex systems. We also discuss the interplay of our results with questions of synchronization, and point out key directions of future research.\\[4pt] Work done in collaboration with Yang-Yu Liu, Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University and Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Albert-L\'aszl\'o Barab\'asi, Center for Complex Network Research and Departments of Physics, Computer Science and Biology, Northeastern University; Center for Cancer Systems Biology, Dana-Farber Cancer Institute; and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School. [Preview Abstract] |
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