Tuberculosis continues to afflict millions of people and causes over a million deaths a year worldwide. Multi-drug resistance is also on the rise, causing concern among public-health experts. This talk will give an overview of my work on modeling tuberculosis at various scales. On the cellular side I will describe models of the metabolism of M. tuberculosis, where insights from duality led to a consistent analysis of existing models, a systematic method for reconciling discrepant models, and the identification of putative drug targets. On the population side I will describe models of strain evolution, where a new metric combined with an optimization-based approach resulted in an accurate classification of complex infections as originating from mutation or mixed infection, as well as the identification of the strains composing these complex infections.

Giant lipid vesicles are closed compartments consisting of semi-permeable shells, which isolate femto- to pico-liter quantities of aqueous core from the bulk. Although water permeates readily across vesicular walls, passive permeation of solutes is hindered. In this study, we show that, when subject to a hypotonic bath, giant vesicles consisting of phase separating lipid mixtures undergo osmotic relaxation exhibiting damped oscillations in phase behavior, which is synchronized with swell–burst lytic cycles: in the swelled state, osmotic pressure and elevated membrane tension due to the influx of water promote domain formation. During bursting, solute leakage through transient pores relaxes the pressure and tension, replacing the domain texture by a uniform one. This isothermal phase transition—resulting from a well-coordinated sequence of mechanochemical events—suggests a complex emergent behavior allowing synthetic vesicles produced from simple components, namely, water, osmolytes, and lipids to sense and regulate their micro-environment. 

In this talk, we study continuous maximal regularity theory for a class of degenerate or singular differential operators on manifolds with singularities. Based on this theory, we show local existence and uniqueness of solutions for several nonlinear geometric flows and diffusion equations on non-compact, or even incomplete, manifolds, including the Yamabe flow and parabolic p-Laplacian equations. In addition, we also establish regularity properties of solutions by means of a technique consisting of continuous maximal regularity theory, a parameter-dependent diffeomorphism and the implicit function theorem.