帝王会所

Quantitative Biology Institute research projects feature statistical, mathematical or computational modeling of biological systems at all levels of complexity, from molecules to ecosystems. All projects are interdisciplinary in nature, conducted by individuals or teams of individuals who combine knowledge of biology with analytic approaches from mathematics, physics or engineering.

Collaborative and Quantitative Biology Projects

Diego Alvarado-Serrano (OHIO, QBI), Robert P. Anderson, New York University,
A novel conceptual framework for integrative ecological and evolutionary inference in dynamic biogeography

Summary: The distribution of species through space and time is driven by a dynamic interaction between ecological and evolutionary processes. Understanding their interaction requires an operational conceptual framework capable of simultaneously incorporating short-time abiotic and biotic ecological interaction and long-term evolutionary drivers of population variation. Here, we propose to expand upon a recently theoretical framework aimed at predicting the probability of presence of species in island systems by integrating population genetic models and genomic data to incorporate key evolutionary processes (e.g., natural selection, genetic drift, and gene flow). This novel framework will contribute to understanding biodiversity patterns, elucidating historical drivers of species and genetic diversity, and ultimately improving our ability to forecast biodiversity trajectories under environmental change.

Winfried Just (OHIO, QBI) and Mario Grijalva (OHIO-HCOM)
Strategies for controlling the spread of Chagas disease by limiting triatomine infestation of housing units

We studied optimal strategies for controlling infestation of housing units by triatomines, which are disease vectors that spread Chagas disease to humans. We found that insecticide spraying is most cost-effective in the long run if the initial treatment is sufficiently aggressive. These predictions were found to be robust for several different model structures.

Publications:

• B. Oduro, M. Grijalva, and W. Just (2018). Models of disease vector control: When can aggressive initial intervention lower long-term cost? . 
• B. Oduro, M. Grijalva, and W. Just (2019). A model of insect control with imperfect treatment. 

OHIO graduate students involved: Bismark Oduro (OHIO Math)

Winfried Just (OHIO, QBI) and Joan Salda帽a, University of Girona, Spain
The interplay between spread of a disease and human reactions to the outbreak

We studied ODE models of epidemic spreading with a preventive behavioral response that is triggered by awareness of the infection, focusing on the question  whether this type of response is sufficient to prevent future flare-ups from low endemic levels if awareness is assumed to decay over time. In the ODE context, our results show that such flare-ups are ruled out in Susceptible-Aware-Infectious-Susceptible models with a single compartment of aware hosts, but can occur if we consider two distinct compartments of aware hosts who differ in their willingness to alert other susceptible hosts.

Publications:

• W. Just, J. Salda帽a, and Y. Xin (2018). Oscillations in epidemic models with spread of awareness. .

OHIO graduate student involvement: Jing, Xin, Mathematics, now postdoc at Johns Hopkins University.

Winfried Just (OHIO, QBI) and David Gerberry (Xavier University)
Factors that influence people鈥�s decisions to get vaccinated against the seasonal flu

Studies of voluntary vaccination decisions by rational individuals predict that  vaccination coverage will remain below the societal optimum, even when imitation of successful others was considered in addition to rational decision-making. However, previous research had almost exclusively used so-called Fermi functions for modeling the probabilities of switching to another strategy. We considered  a more general functional form of the switching probabilities that is consistent with empirical data in psychological experiments and involves one additional parameter that can be loosely interpreted as a degree of open-mindedness. We found  that sufficiently high degrees of open-mindedness will drive the  vaccination coverage above the Nash equilibrium for rational decision-making and arbitrarily close to the societal optimum.

Publications:

• Y. Xin, D. Gerberry, and W. Just (2019). Open-minded imitation can achieve near-optimal vaccination coverage.

Francois Brajot (QBI) and Alexander Neimann (QBI)
Multisensory integration in speech production (2018 鈥� present)

The voice exhibits temporal fluctuations on various time scales. This project aims to characterize the interaction of somatosensory and auditory feedback in speech and determine physiological and dynamical mechanisms responsible for oscillatory instabilities of the voice. One example is vocal tremor showing fluctuations in the range 4-7 Hz resulting presumably from somatosensory feedback. Another example is vocal wow, slower fluctuations at frequencies below 2 Hz, attributed to auditory feedback. These distinct fluctuations have important implications for diagnosing and treating neurological disorders, but the underlying mechanisms remain poorly understood. We use a combination of experimental, advanced time-series analysis and modeling to study mechanism underlying fluctuations in speech.

Graduate student involvement: Samantha Davis, Hearing, Speech, and Language Sciences

Publications:

• FX Brajot, AB Neiman, 鈥溾��, The Journal of the Acoustical Society of America 147 (3), 1822-1833 (2020).

Alexander Neimann (QBI) and Peter Tass, Stanford University, (2019 鈥� present)
Structural and spike-timing dependent plasticity in brain networks

Peripheral sensory neurons may possess tree-like myelinated dendritic terminals at receptive fields, with multiple nodes of Ranvier. Examples include the afferent innervation of muscle spindles, pain receptors, cutaneous mechanoreceptors, and electroreceptors in paddlefish. We study the collective dynamics and information transfer in diffusively coupled excitable elements on small tree networks with connectivity, as a model of such sensory neurons. We use a combination of analytical and numerical techniques to address important questions on how the collective spiking activity emerges, how the natural randomness of dendritic topology is reflected in the variability of neuronal firing, and how the topological randomness affects the coding of sensory stimuli.

Graduate student involvement: Kanishk Chauhan (OHIO Physics).

Alexander Neimann (QBI) and Lutz Schimansky-Geier, Humboldt University Berlin, Germany
Variability and information coding in random trees of excitable elements鈥� (2016 鈥� 2019)

The goal was to establish mechanisms of spike generation and information coding in sensory neurons with myelinated dendrites.

Graduate students involved: Ali Khaledi Nasab (OHIO, physics), Justus Kromer (Humboldt University, physics)

Publications:

• A Khaledi-Nasab, JA Kromer, L Schimansky-Geier, AB Neiman, 鈥溾��, Physical Review E 98 (5), 052303 (2018).
• J Kromer, A Khaledi-Nasab, L Schimansky-Geier, AB Neiman, 鈥淓mergent stochastic oscillations and signal detection in tree networks of excitable elements鈥�, .
• JA Kromer, L Schimansky-Geier, AB Neiman, 鈥淓mergence and coherence of oscillations in star networks of stochastic excitable elements鈥�,

David Tees (QBI) and Monika Burdick(Bioengineering)
Characterization of mechanical properties of cancer stem cells

All cancer cells show some characteristics of the characteristics of stem-cells, but it has become evident in recent years that some cancer stem cells are more differentiated (and less stem-like) than others. Less-differentiated (more stem-like) cells are found to be more invasive and tumorigenic than less-differentiated cells. The biochemical characterization of more stem-like cells had been extensively studied, but the resulting changes to physical properties could also be useful as a means of detecting and isolated more-stem-like cells. The Tees lab has used micropipette aspiration and has developed microfluidic devices to characterize breast cancer cell lines in terms of their mechanical properties. This work has been done in collaboration with Dr. Monica Burdick's lab in the Department of Chemical and Biomolecular Engineering. The work was supported by an NSF grant that ended near the beginning of the five-year review period, but the work has continued. There have been a number of applications for NIH SBIR grants with the company Nanohmics that would build on this work. There have been two papers from the Tees lab on this work during the five-year period as well as a master's thesis (Pooja Chopra) and an undergraduate thesis (Brandon Niese).

Donald B Miles (QBI) and Jean Clobert and Alexis Rutschmann (Station d'Ecologie Th茅orique et Exp茅rimentale SETE (CNRS & Universit茅 Toulouse Paul Sabatier)
Predicting species responses to climate change

Miles is working with Drs. Jean Clobert and Alexis Rutschmann on a project predicting species responses to climate change. They have genomic data for over 1,000 individuals of the species Zootoca vivipara. They also have physiological and life history data. They are applying quantitative genomic models to investigate the heritability of physiological traits that are assumed to enhance the persistence of species in a warmer environment.

Alexander Govorov (QBI) and Tim Liedl (Ludwig Maximilian University, Munich, Germany)
DNA-assembled nanostructures with unique optical properties

The ongoing collaboration between Govorov鈥檚 group at OHIO and the Munich team concerns the optical properties of DNA-assembled nanostructures. This collaboration is built on the complementary expertise of the groups. The Munich group is a world leader in DNA nano-assembly. Simultaneously, Govorov鈥檚 group is recognized for its computation work in optical properties of nanostructures. Over the last years, the groups received two grants from the Volkswagen Foundation supporting their collaboration. Overall, the joint research has led to several publications in high-profile journals, such as Nature Physics, ACS Nano, ACS Energy Letters, Nano Letters. To give an example, one of the joint papers (below) describes a new mechanism of energy transfer in plasmonic nanocrystal chains assembled using the DNA-origami technique. 

• E.-M. Roller, L.V. Besteiro, C. Pupp, L. Khosravi Khorashad, A. O. Govorov, T.Liedl, , Nature Physics, 13, 761-765 (2017).

Peter Jung (QBI) and Tony Brown (OSU Wexner Medical Center) (2002 鈥� present)
Dynamic Regulation of Axonal Morphology by Neurofilament Transport

The function of nervous systems is dependent on the rapid propagation of action potentials along axons, which is in turn dependent on axon size and shape. A principal determinant of axon size and shape in vertebrates are space-filling cytoskeletal polymers called neurofilaments (NFs). However, NFs are also cargoes of axonal transport that move in a rapid intermittent manner along microtubule tracks. Thus NFs define axonal morphology, but they are also in constant flux. The proposed research addresses this intriguing and physiologically important relationship. A key question is how do myelinated axons develop and maintain their correct morphology? The central hypothesis of this proposal is that the kinetics of NF transport determines axonal NF content, which in turn specifies axonal caliber. A new and transformative view is proposed in which axon morphology is not a passive feature of axons but is actively and dynamically regulated by the movement of these structural elements. This perspective may also have broader implications for understanding the mechanisms that cause the excessive NF accumulations and gross distortions of axonal morphology observed in many neurodegenerative diseases.

Most recent graduate student involvement:

• Tung Nguyen, graduated  2018, Thesis: Computational Modeling of Slow Neurofilament Transport along Axons
• Chris Johnson, graduated 2016, Thesis: Investigating the Slow Axonal Transport of Neurofilaments: A Precursor for Optimal Neuronal Signaling
• Undergrads: Anika Friedman, Honor鈥檚 thesis: A Computational Model of Neurofilament Kinetics Relating Axonal Caliber Growth and the Neurofilament Slowing Phenomenon

Recent publications

• Boyer NP, Azcorra M, Jung P, Brown A. . J Vis Exp. 2020 Aug 31;(162). doi: 10.3791/61264. PMID: 32925891.
• M.V. Ciocanel, P. Jung, and A. Brown. . Mol Biol Cell, E19090509 (2020)
• C. L. Walker, A. Uchida, Y. Li, N. Trivedi, J. D. Fenn, P. C. Monsma, R. C. Lariviere, J.-P. Julien, P. Jung, and A. Brown. . J Neurosci, 39(4):663鈥�677 (2019)

Funding for project (third round of continuous NSF funding)

Collaborative Research: Role of Neurofilament Transport in the Growth of Axonal Caliber, National Science Foundation, Jung, P., $345,000.00, May 1, 2017 - June 30, 2021.

Peter Jung (QBI) and Subhoit Roy (UC San Diego)
Bulk actin transport in axon

Classic pulse-chase studies have shown that actin is conveyed in slow axonal transport, but the mechanistic basis for this movement is unknown. Recently, we reported that axonal actin was surprisingly dynamic, with focal assembly/disassembly events ("actin hotspots") and elongating polymers along the axon shaft ("actin trails"). Using a combination of live imaging, superresolution microscopy, and modeling, in this study, we explore how these dynamic structures can lead to processive transport of actin. We found relatively more actin trails elongated anterogradely as well as an overall slow, anterogradely biased flow of actin in axon shafts. Starting with first principles of monomer/filament assembly and incorporating imaging data, we generated a quantitative model simulating axonal hotspots and trails. Our simulations predict that the axonal actin dynamics indeed lead to a slow anterogradely biased flow of the population. Collectively, the data point to a surprising scenario where local assembly and biased polymerization generate the slow axonal transport of actin without involvement of microtubules (MTs) or MT-based motors. Mechanistically distinct from polymer sliding, this might be a general strategy to convey highly dynamic cytoskeletal cargoes.

Publications:

• N. Chakrabarty, P. Dubey, Y. Tang, A. Ganguly, K. Ladt, C. Leterrier, P. Jung, and S. Roy. . J Cell Biol, 218(1):112鈥�124 (2019)
• N. Chakrabarty and P. Jung. . Phys Biol, 16(5):056001, (2019).

Todd Young (QBI) and Erin Murphy (HCOM, OU)
Validation of pathogen recovery from ventilator filters (2015-2018)

Laboratory project to determine the reliability of detection of bacterial pathogens from ventilator circuit filters. Filters were inoculated with varying levels of a variety of common pathogens. Results from Quantitative PCR were compared with inoculation levels.

Involved undergraduate students: Kara Findley and Phillip Miller (HCOM)

Graduate student: Xue Gong (Math)

Funded by Heritage College of Oesteopathic Medicine, Research & Scholarly Affairs Com- mittee (RSAC), PI: Erin Murphy, co-PI: T.Y.. 7/1/14 - 6/30/17, $10,000.

Todd Young (QBI) and E.M Bocko (OU, Math)
Early Treatment Gains for Antibiotic Administration and Within Human Host Time Series Data (2015-2017)

We used patient time series data and dynamical models to predict the gains in patient out- comes by early detection of the presence of bacterial pathogens. Data for sample collected from ventilated ICU patients were used to inform models of pathogen growth and decrease due to treatment. A mathematical model was proposed to predict the extent to which early detection and lead to early recovery.

Funding: This work was an outgrowth of a project that was funded by an internal grant at Vanderbilt University Medical School on early detection of Ventilator Associated Pneumonia.

Publications:

• , E.M. Boczko, T.R. Young, Mathematics in Medicine & Biology 35 (2018), 203鈥�224. doi:10.1093/imammb/dqw025

Todd Young and Scott Hooper
The Altered Van der Pol Oscillator and Stomatogastric Ganglion (2019 鈥� present)

We introduced a slow moving parameter into a common dynamical model of neuron firing in order to understand how inherently slow-firing neurons are able to cycle rapidly as part of a network. The adapted model was compared with data from the Pyloric Network in the Stomatogastric Ganglion in Lobsters.

Involved students: Kevin Promorsksi (Mathematics).

Todd Young (QBI), Jan RomboutsKU Leuven, Leuven, Belgium and Bal`azs B`ar`any, Department of Stochastics, Budapest University of Technology and Economics, Budapest, Hungary
Clustering in Population Models of Cell Cycle Dyanamics (2014 鈥� present)

This work is a continuation of a project begun with Erik Boczcko, Dept. Biomedical Informatics, Vanderbilt University that was funded by 鈥淒ynamics and Bifurcations of Population Structures Induced by Cell Cycle Feedback鈥� Joint DMS/NIGMS Initiative to Support Re- search in the Area of Mathematical Biology grant NIH-NIGMS R01GM090207. 08/2009 - 07/2013. PI: Erik Boczko, Vanderbilt Medical Center. Project Total: $1,234,454. Project funding to 帝王会所 $256,976.

This project has involved many undergraduate and graduate students. It received some funding from QBI for summer work by undergraduate students and resulted in many publications.

Mitchel Day (QBI)
Neural coding of sound source location across the frequency spectrum

A "division of labor" has previously been assumed in which the directions of low- and high-frequency sound sources are thought to be encoded by neurons preferentially sensitive to low and high frequencies, respectively. Contrary to this, we found that auditory midbrain neurons encode the directions of both low- and high-frequency sounds regardless of their preferred frequencies. We determined this by quantifying information transmitted by neurons about sound source location using information theory, separately for low- and high- frequency sounds. Neural responses were shaped by different sound localization cues depending on the stimulus spectrum--even within the same neuron.

Publications:

• Dorkoski R, Hancock KE, Whaley GA, Wohl TR, Stroud NC, Day ML. . J Neurophysiol. 2020 May 1;123(5):1791-1807. doi: 10.1152/jn.00713.2019. Epub 2020 Mar 18. PMID: 32186439; PMCID: PMC7444926.

Mitchel Day (QBI)
Effects of sensorineural hearing loss on the neural coding of sound source location

Sensorineural hearing loss compromises perceptual abilities that arise from hearing with two ears, such as sound localization, yet its effects on binaural aspects of neural responses are largely unknown. We found that, following severe hearing loss because of acoustic trauma, auditory midbrain neurons specifically lost the ability to encode time differences between the arrival of a noise stimulus to the two ears (a major cue for sound localization), whereas the encoding of sound level differences between the two ears (the other major cue for sound localization) remained uncompromised. We determined this by quantifying information transmitted by neurons about sound source location using information theory and compared between normal-hearing and hearing-loss groups.

Publications:

• Haragopal H, Dorkoski R, Pollard AR, Whaley GA, Wohl TR, Stroud NC, Day ML. J Neurophysiol. 2020 Oct 1;124(4):1165-1182. doi: 10.1152/jn.00349.2020. Epub 2020 Aug 26. PMID: 32845200; PMCID: PMC7717161.

Graduate students: H. Haragopal (BIOS)

Undergraduate students: GA Whaley, NC Stroud

Scott L Hooper (QBI) and A. B眉schges (Universit盲t zu K枚ln, Germany)
Neurobiology of Motor Control (2007 鈥� present)

Publications:

• (2017) SL Hooper, A B眉schges, eds. Wiley Blackwell, Hoboken NJ

Fuh-Cherng Jeng
Influence of Maternal Drug Use on Neonatal Maturity of the Auditory System

This study involves faculty members in HCOM Pediatrics department at 帝王会所.

Funding: Advancing Scholarship in Research and Education (ASPIRE), College of Health Sciences and Professions at 帝王会所. (6/1/2019 鈥� 5/30/2021).

Fuh-Cherng Jeng
Computer Modeling of Brainstem Responses to Voice Pitch in American and Chinese Neonates

This study involved faculty members at the ENT Department at China Medical University Hospital in Taiwan.

Funding: Baker Fund Award, 帝王会所. (12/15/2014 鈥� 6/30/2016)