2015 Summer Undergraduate REU Program

Indiana University - Purdue University Indianapolis

IUPUI - Department of Physics

Topic 1:

A Bacterial Serengeti - Steve Presse

Project Description:

The African Serengeti is a wonder of the natural world. Populations of gazelles, zebras and buffalos, all of which are unmatched in number, migrate through its high grass under the watchful eye of some of the fiercest predators on the planet. Both predators and prey rely on their sense of vision, amongst other senses, to survive. At a much smaller scale, microscopic participants are waging an equally critical battle for survival. Here we are talking about a length scale a few hundredths of the width of a human hair. The battle is taking place on the surface of your phone, your gut and many other places as we speak. This battle is happening between individual unicellular organisms. Unlike the Serengeti, these predators and prey do not have eyes yet theirs is an equally ruthless war.

For example, your white blood cells chase after and 'eat' bacteria; bacteria of different strains attack one another. Also, when food is scarce, some bacterial species behave as predators treating other bacteria as prey. Chemotaxis is the bacterial equivalent of having eyes. It is the process by which cells sense small molecules in their environment through the chemoreceptors at their surface. These small molecules fall into two categories: chemorepellents or chemoattractants. When these small molecules bind to the chemoreceptors on the surface of bacteria this induces complicated signaling events inside the bacteria which ultimately results in these actions: bacteria move towards chemoattractants or away from chemorepellents.

The world of chemotaxis is widely studied in biology and the signaling events responsible for bacterial chemotaxis are well understood for some bacteria. There are numerous mathematical and physical mod-els for how bacteria sense their environment and subsequently choose to move. One common model assumption is to say that chemorepellents or chemoattractants are present in large numbers. Therefore bacteria can sense a change of concentration in time of the small molecules and respond accordingly.

Our work is focused on bacterial predator-prey interactions. Here the prey generates small molecules which we believe the predator uses to track it. However, the concentration of chemoattractant released by the prey is small. Therefore the predator has to ‘make up its mind’ on the basis of little information. For instance, the predator may spend a short while receiving little signal just because these chemoattractants are present in such small quantities. What should the predator do then? Does it switch directions and look elsewhere or does it continue following a straight path? What is the best strategy for finding prey?

One very bad strategy for the predator is to ignore signal from the prey and search for the prey at random. Another very bad strategy is for the predator to be stubborn and follow one straight path on the basis of very limited information. The best strategy is a compromise between these two. Here are other interesting questions: do predators repel each other? Do bacterial prey warn other bacteria, through chemical sensing, that a predator is around? We would like to address these questions by watching populations of bacteria interact. This work is collaborative between experiment and theory in the Physics Department. We do cell culturing, cell tracking, data analysis, write down mathematical models and numerically assess our models.

[1] Kress H. et al. 2009. Cell stimulation with optically manipulated micro sources. Nature Methods, 6, 905-909.

IUPUI - Department of Mathematical Sciences

Topic 2:

Respiratory-sympathetic coupling in neurogenic hypertension - Yaroslav Molkov

Project Description:

Chronic exposure to intermittent hypoxia (CIH) that occurs in obstructive sleep apnea is the main factor leading to sympathetic overactivity and hypertension. A CIH-driven increase in sympathetic output is largely dependent on the emergence of an active expiratory pattern. The respiratory central pattern generator (rCPG) is composed of two interacting oscillators. The first occupies Bötzinger/pre-Bötzinger complexes and generates self-sustained respiratory rhythm controlling the diaphragm to provide inspiration. The second oscillator, the parafacial respiratory group (pFRG), resides in the retrotrapezoid nucleus (RTN). The RTN/pFRG oscillations emerge in hypoxic and hypercapnic conditions, and drive motor output to abdominal muscles for active (forced) expiration. Interactions of these respiratory circuits with the sympathetic neurons of the rostral and caudal ventrolateral medulla evoke respiratory-related oscillations in sympathetic efferent drive. Exposure to CIH leads to alterations in excitability of RTN/pFRG neuronal population and/or modifications in synaptic connections between respiratory oscillators and sympathetic neurons that ultimately results in the elevated baseline sympathetic activity and arterial pressure. This interdisciplinary project aims to reveal the mechanisms that couple breathing and control of blood pressure in the brain in health and disease, and for the first time translate them into a realistic computational model. Such a model will have unprecedented potential for generating an effective non-pharmacological means of controlling blood pressure and breathing via implantable biofeedback devices and non-invasive devices for guided control of autonomic function. Furthermore, it will provide a robust scientific substrate for evaluating the usefulness and safety of alternative and complementary medicine interventions, such as controlled breathing practices (e.g. through meditation and yoga), for lowering blood pressure and improving heart rate variability. Students will be involved in model development, coding, simulation, and statistical analyses of experimental comparisons.