We introduce and analyze a mathematical model for the regeneration of planarian flatworms. This system of differential equations incorporates dynamics of head and tail cells which express positional control genes that in turn translate into localized signals that guide stem cell differentiation. Orientation and positional information is encoded in the dynamics of a long range wnt-related signaling gradient.
We motivate our model in relation to experimental data and demonstrate how it correctly reproduces cut and graft experiments. In particular, our system improves on previous models by preserving polarity in regeneration, over orders of magnitude in body size during cutting experiments and growth phases. Our model relies on tristability in cell density dynamics, between head, trunk, and tail. In addition, key to polarity preservation in regeneration, our system includes sensitivity of cell differentiation to gradients of wnt-related signals measured relative to the tissue surface. This process is particularly relevant in a small tissue layer close to wounds during their healing, and modeled here in a robust fashion through dynamic boundary conditions.[-]

Dynamic Energy Budget (DEB) models describe how individual organisms acquire and use energy from food and have therefore been argued to consistently link different levels of biological organisation. Various types of DEB models, differing in the organisation and precedence of metabolic processes such as growth, maintenance and reproduction, have been proposed and investigated, although recently the term DEB theory has become more and more identified with the framework developed by Kooijman.
In this lecture I will address the question to what extent differences between DEB models affect the dynamics at the population and community level. I will show that maintenance costs, which are accounted for in all DEB models, have a crucial influence, but that metabolic organisation is of lesser importance. I will furthermore show that population and community dynamics are mostly determined by differences in the capacity of individuals with different body sizes or in different stages of their life history to transform food into new biomass. Such differences, which I refer to as ontogenetic asymmetry in energetics, are however influenced more by the types of food that individuals forage on in different stages of their life history than by their internal energetics. Ontogenetic shifts in resource use during life history are therefore likely to have a larger influence on population and community dynamics than the details of the individual energy budget.[-]

How combination therapies can reduce the emergence of cancer resistance? Can we exploit intra-tumoral competition to modify the effectiveness of anti-cancer treatments?
Bearing these questions in mind, we present a mathematical model of cancer-immune competition under therapies. The model consists of a system of differential equations for the dynamics of two cancer clones and T-cells. Comparisons with experimental data and clinical protocols for non-small cell lung cancer have been performed.
In silico experiments confirm that the selection of proper infusion schedules plays a key role in the success of anti-cancer therapies. The outcomes of protocols of chemotherapy and immunotherapy (separately and in combination) differing in doses and timing of the treatments are analyzed.
In particular, we highlight how exploiting the competition between cancer populations seems to be an effective recipe to limit the insurgence of resistant populations. In some cases, combination of low doses therapies could yield a substantial control of the total tumor population without imposing a massive selective pressure that would suppress the sensitive clones leaving unchecked the clonal types resistant to therapies.[-]

Evolutionary rescue (ER) is the process by which a population, initially destined to extinction due to environmental stress, avoids extinction via adaptive evolution. One of the widely observed pattern of ER (especially in the study of antibiotic resistance) is that it is more likely to occur in mild than in strong stress. This may be due either to purely demographic effects (extinction is faster in strong stress) or to evolutionary effects (adaptation is harder in strong stress). Disentangling the two and predicting the likelihood of ER has important medical or agronomic implications, but also has a strong potential for empirical testing of eco-evolutionary theory, as ER experiments are widespread (at least in microbial systems) and fairly rapid to perform.
Here, I will present results from three recent articles [1-3] where we considered the probability of ER, and the distribution of extinction times, in a classic phenotype-fitness landscape: Fisher's geometric model (FGM). In our (classic) version of the FGM, fitness is a quadratic function of traits, with an optimum that depends on the environment. This model has received some empirical support with respects to its ability to reproduce or even predict patterns of context dependence in mutation effects on fitness (be it environmental or genetic context).
In our FGM-ER scenario, a population is initially adapted to the current optimum (either a clone or at mutation selection balance). The environment shifts abruptly and the optimum position, plus possibly peak height and width are modified. We follow the evolutionary and demographic response to this change, assuming a density-independent demography (which we approximate by continuous branching process CB process or Feller process).
In spite of its simplicity, the FGM displays fairly distinct behaviors depending on the relative strength of selection and mutation: this yields different approaches to deal with the FGM-ER scenario. I will thus present the different approaches we have used so far: from the strong selection, weak mutation regime to the weak mutation strong selection regime, and discuss possible extensions at the transition between these regimes.[-]

We consider stochastic models of scalable biological reaction networks in the form of continuous time pure jump Markov processes. The study of the mean field behavior of such Markov processes is a classical topic, with fundamental results going back to Kurtz, Athreya, Ney, Pemantle, etc. However, there are still questions that are not completely settled even in the case of linear reaction rates. We study two such questions. First is to characterize all possible rescaled limits for linear reaction networks. We show that there are three possibilities: a deterministic limit point, a random limit point and a random limit torus. Second is to study the mean field behavior upon the depletion of one of the materials. This is a joint work with Lai-Sang Young.[-]