AMPK and mTOR Impose Dualistic Regulation of Mitophagy and Autophagy in In Vitro Models of Prostate Cancer

Prostate cancer is the abnormal growth and proliferation of previously normal cells of the prostate and has the second highest incidence in men worldwide. Physiologic manipulation of AMP-activated protein kinase (AMPK), a highly conserved enzyme responsible for regulation of energy homeostasis during metabolic stress, is a potential treatment, especially for metastatic, castration-resistant prostate cancers. AMPK is a known inhibitor of the enzyme mTOR, the final enzyme in the PKT/AKT/mTOR pathway responsible for cell growth and proliferation signaling. The hypothesis of this project is that activation of AMPK leads to increased mTOR-dependent mitophagy and subsequent autophagy in prostate cancer cells. The overall aim of this project is to establish a role between activated AMPK and mTOR dependent mitophagy and autophagy. Although preliminary data remains inconclusive, future research is promising

A Computational View on Natural Evolution: On the Rigorous Analysis of the Speed of Adaptation

Inspired by Darwin’s ideas, Turing (1948) proposed an evolutionary search as an automated problem solving approach. Mimicking natural evolution, evolutionary algorithms evolve a set of solutions through the repeated application of the evolutionary operators (mutation, recombination and selection). Evolutionary algorithms belong to the family of black box algorithms which are general purpose optimisation tools. They are typically used when no good specific algorithm is known for the problem at hand and they have been reported to be surprisingly effective (Eiben and Smith, 2015; Sarker et al., 2002). Interestingly, although evolutionary algorithms are heavily inspired by natural evolution, their study has deviated from the study of evolution by the population genetics community. We believe that this is a missed opportunity and that both fields can benefit from an interdisciplinary collaboration. The question of how long it takes for a natural population to evolve complex adaptations has fascinated researchers for decades. We will argue that this is an equivalent research question to the runtime analysis of algorithms. By making use of the methods and techniques used in both fields, we will derive plenty of meaningful results for both communities, proving that this interdisciplinary approach is effective and relevant. We will apply the tools used in the theoretical analysis of evolutionary algorithms to quantify the complexity of adaptive walks on many landscapes, illustrating how the structure of the fitness landscape and the parameter conditions can impose limits to adaptation. Furthermore, as geneticists use diffusion theory to track the change in the allele frequencies of a population, we will develop a brand new model to analyse the dynamics of evolutionary algorithms. Our model, based on stochastic differential equations, will allow to describe not only the expected behaviour, but also to measure how much the process might deviate from that expectation