2020 Seminars

Prof. Navid Ghaffarzadegan (Industrial & Systems Engineering, Virginia Tech)

"Systems sciences, behavioral complexities, and the challenge of dynamic modeling of the spread of covid-19"

Mathematical modeling is essential for understanding the spread of an infectious disease and developing proper policies to contain it. In the case of covid-19, however, we are dealing with a unique complex situation that requires revisiting conventional models and including several dynamic and behavioral mechanisms that are specific to this novel virus. To mention a few characteristics: 1) A large fraction of covid-19 patients are asymptomatic and undiagnosed, 2) the virus is novel thus it seems that almost all human population are susceptible, 3) there is a considerable delay between exposure to the virus and the symptom onset, 4) risks are high; the infected fatality rate is considerable, 5) test capacities and their accuracy are limited, and 6) public risk perception has been changing and it influences people's behavior. Therefore, from a systems science perspective, we are dealing with a complex system that is only partially observable with considerable delays and inaccuracy, and our observations are influencing the (human-side of the) system. To elaborate this point, I will offer three examples of my recent modeling efforts, in collaboration with several colleagues. First, I will offer an example of how the number of unknown cases of covid-19 can be estimated using a dynamic simulation model; second, I will report on a project to estimate the impact of weather on the transmission of the disease; and third, I will offer a model of estimating the spread of covid-19 in universities and optimal university-level policies to contain the disease. Finally I will reflect on these experiences from a systems science point of view and complexity theories.

Host: Uwe Tauber

Dr. Tatiana Rostovtseva (National Institutes of Health)

"A mitochondrial throttle: lipid-mediated protein complexes at the mitochondrial surface"

Mitochondria are organelles found in virtually all eukaryotic cells. Mitochondria are not only “the powerhouse of the cell” but are also involved in multiple crucial cellular functions. Mitochondrial dysfunction plays a central role in a wide range of age-related disorders, neurodegenerations, and cancer. Mitochondria are composed of two membranes. The inner membrane plays a prominent role in power production via oxidative phosphorylation, while the mitochondrial outer membrane (MOM) acts as a “throttle”, controlling the access of metabolites to the inner membrane and thus the rate of energy production. A significant portion of the control functions is carried on by the voltage-dependent anion channel (VDAC), a passive transport channel which allows water soluble metabolites and ions to cross MOM. Recent findings uncover an efficient regulatory mechanism of this channel through its interactions with cytosolic proteins. One such regulator is α-synuclein (αSyn), the intrinsically disordered neuronal protein highly expressed in nervous system and associated with Parkinson’s Disease pathology. αSyn is directly involved in mitochondrial dysfunction in neurodegeneration. Probing the interactions of αSyn with VDAC nanopore by single-channel recordings we showed that αSyn induces transient blockages of the ionic current through the channel; identified as the insertion and escape of the unstructured charged C-terminal tail of αSyn into the channel in response to a transmembrane potential. The discovery of this novel regulatory mechanism of mitochondrial respiration has raised several fundamental biophysical questions, including a mechanism of αSyn transient blockage of the VDAC nanopore and translocation through it, and what role mitochondrial lipids assume in mediating the αSyn-VDAC interaction. In this talk, I will discuss of how we answer these questions by using a combination of single-molecule electrophysiology, theoretical modeling, and macroscopic biophysical studies of αSyn binding to planar and liposome membranes. The VDAC nanopore thus proves to be extremely sensitive single-molecule probe for peripheral membrane protein interaction with integral membrane proteins of mitochondria. This study could be important for the structure-inspired design of mitochondria-targeting agents.

Host: Rana Ashkar

Prof. Carla Finkielstein (Fralin Biomedical Research Institute at Virginia Tech Carilion)

Emerging opportunities in cancer chrono-therapy

Previously, cancer treatment modalities relied primarily on chemotherapeutic agents; nowadays, advances in rationally-designed drugs and targeted therapies have enabled the manipulation of cancer-specific molecules and cancer regulators that are frequently mutated and globally identified in various cancers. Regardless of the approach, the objective of controlling cancer progression has always been to attenuate, eliminate, or control then eomorphic activity of target driver mutations in tumors by maintaining steady levels of therapeutic agents. As precision medicine gains momentum, so does the possibility of customizing individual patients’ treatments to the “time-of-day” when tumor cells exhibit the highest susceptibility to therapeutics (1). However, a gap exists in our knowledge regarding the times at which therapeutically-targeted molecules are likely to be most susceptible to drugs and yield the greatest cellular effect. As a result, there is a need to unveil “when” and “where” druggable targets are in the cell and “to what extent” the tumor’s time-keeping system differs from normal tissue. Defining priorities that address those needs across the hierarchical system of organization will allow researchers to find the best time-windows where delivery of treatment modalities can be most effective.

Host: Uwe Tauber

Prof. Jiajia Zhou (Beihang University, Beijing,China)

"Onsager variational principle and its applications in soft matter systems"

Onsager principle is the variational principle proposed by Onsager in his celebrated paper on the reciprocal relation. The principle is useful not only in deriving many evolution equations in soft matter systems, it is also useful in solving such equations approximately. Three examples are discussed: the capillary filling and rising, the stratification in binary colloidal solutions, and the viscoelasticity of polymer solutions. These examples show that the method can give new perspectives of the essential dynamics in soft matter systems.

Host: Shengfeng Cheng

Dr. James McClure (Research Computing, Virginia Tech)

"Modeling multi-phase flow and anomalous diffusion with mesoscopic methods" 

Lattice Boltzmann methods provide a practical bridge between molecular- and continuum-scale models, relying on quasi-molecular interaction rules to simulate physics at significantly larger length and time scales compared to what is accessible from molecular dynamics. This talk will review approaches to develop mesoscopic models using the lattice Boltzmann method, with applications to wetting and spreading on heterogenous surfaces, fluid flow in porous media, and diffusion in electrochemical cells. Using simulation data, we consider how time-and-space averaging can be applied to understand scale effects in heterogeneous systems, particularly for long-wavelength fluctuations in non-equilibrium systems. Consequences for symmetry-breaking are explored within this context.

Host: Uwe Tauber

Thanksgiving Break (No Seminar)

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"Tenure Track Physics Meeting" (No Seminar)

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Prof. Irep Gözen (University of Oslo, Norway)

“Lipid Nanotubes: a possible route to primitive cell formation and growth”

Membrane-enclosed cellular compartments create spatially distinct microenvironments which confine and protect biochemical reactions in the cell. On the early Earth, the autonomous formation of compartments is presumed to have enabled encapsulation of nucleotides, satisfying a starting condition for the emergence of life. Recently, surfaces have become into focus as potential platforms for the self-assembly of prebiotic compartments, as notably enhanced vesicle formation was reported in the presence of solid interfaces. The detailed mechanism of such formation at the mesoscale however is still under discussion. I will describe the spontaneous transformation of lipid reservoirs on solid substrates to unilamellar membrane compartments through a sequence of topological changes, proceeding via a network of interconnected lipid nanotubes. We show that this transformation is entirely driven by surface-free energy minimization and does not require hydrolysis of organic molecules, or external stimuli such as electrical currents or mechanical agitation. The compartments grow by taking up the external fluid environment and can subsequently separate and migrate upon exposure to hydrodynamic flow. This may explain, for the first time, the details of self-directed transition from weakly organized bio amphiphile assemblies on solid surfaces to protocells with secluded internal contents.

Host: Prof. Nadir Kaplan

"Spring Break" (No Seminar)

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No Seminar (Due to COVID-19)

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No Seminar (Due to COVID-19)

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No Seminar (Due to COVID-19)

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