Integrating high-dimensional biological data into mechanistic models requires practical identifiability for reliable inference. We develop a computational framework that reveals scaling laws for identifiability via asymptotic analysis, combining Fisher information with perturbed Hessians to quantify identifiability and uncertainty in non-identifiable subspaces. Validated on several benchmark...
Cells invariably encounter unpredictable changes in their microenvironment and adapt by orchestrating substantial alterations in their molecular states. The timescale of molecular adaptation depends on how quickly a cell loses its molecular memory of past environmental encounters through the degradation rate of proteins unfavorable to the current environment. Concurrently, de novo synthesis of...
Cancer cell adaptation to their physical tumor microenvironment is a key driver of malignancy. Recent experimental evolution experiments show that the soft extracellular matrix (ECM) can impose a selection pressure on genetically variable tumor populations. Over months of sustained culture, the selection pressure leads to enrichment of specific genetic variants with high fitness, but the...
In this talk, I will introduce four systems of ODEs to identify the most plausible model and the key reactions governing the dynamics of the tumor microenvironment (TME) in estrogen receptorโpositive (ER+) breast cancer. All models quantitatively fit the experimental data for radiation therapy (RT) and endocrine therapy fulvestrant (Fulv) in TC11 ER+ cells, as well as RT and immune checkpoint...
Recent experimental work has shown that dynein transports cargo faster in vivo than in vitro, although counter intuitive, the results are consistent with other experimental data \cite{Torisawa:2025:AFC}. Typically, it is assumed that the cytoplasm, a more viscous and complex environment, should slow down transport compared to in vitro experiments. It is postulated that the catch bond nature...
Intermediate filament (IF) elongation is driven by the longitudinal annealing of semiflexible biopolymers. Although in vitro assembly is routinely characterized by microscopy and static light scattering (SLS), a unified theoretical framework linking these complementary measurements is lacking. Here, we bridge these modalities using a Smoluchowski coagulation model for semiflexible polymers. We...
Resistance to immune checkpoint inhibitors (ICI), including anti-PD-1 and anti-PD-L1 therapies, remains a major limitation in cancer treatment, with most patients relapsing despite initial responses. Previous studies have shown that inhibition of TNF-alpha or TGF-beta overcome resistance to anti-PD-1. Here, we develop a mathematical model to investigate a mechanism of ICI resistance driven by...
Mathematical modelling and computation allow for quantitative testing of proposed hypotheses and estimation of important physical and biological parameters. Combining experiments with mathematical modelling allows a rigorous validation of model hypotheses, thereby providing a powerful investigation tool in biology and medicine. The focus of this session will be on applications of mathematics...
