Molecular Co-Evolution: Lessons from Pathogen-Immune System Interactions

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

The workshop titled, "Molecular coevolution: lessons from pathogen-immune system interactions", will be held on 11th-12th April 2016, at the Princeton Center for Theoretical Sciences (PCTS). It will bring together theoreticians and experimentalists who study adaptive immunity in vertebrates or in bacteria. Adaptive mechanisms for immunity have evolved to mount a flexible and diverse response and to counteract the rapid evolution of pathogens to enhance organismal survival. The participants of this program work at the cutting edge of research into such immune dynamics. The goal is to foster new collaborations that build and test predictive approaches to coevolution of pathogens and the immune system. Predictive modeling is an essential component for understanding the fundamental science of the immune system. Such basic science advances will eventually enable advances in medicine. Close to half of the participants in this workshop are females, helping to increase diversity and participation of women in STEM fields. The immune systems in vertebrates and in bacteria have evolved remarkable mechanisms for adapting to a diverse and constantly changing pathogenic environments. In vertebrates, new receptors are constantly generated by genomic recombination, and those that successfully detect threats are selectively amplified to protect the host. Some of the stimulated receptors are retained to form a memory of past infections, and thus to mount a rapid response against future infections of a similar type. This process of affinity maturation in an adaptive immune system constitutes a Darwinian evolution of the immune cells that occurs during the lifetime of an organism. By contrast, in some bacteria and archaea, immunity is directly acquired from interactions with the environment, and is heritable to future generations. These bacteria use the CRISPR-Cas mechanism to acquire specific genomic sequences from attacking phages (viruses that attack bacteria), and use these sequences to target future invaders. In both cases, the rapid turnover of pathogens to escape the adaptive immune response creates an evolutionary arms race at the molecular level. Understanding the complex dynamics of these adaptive immune systems in response to coevolving pathogens is only possible through a joint theoretical and experimental effort. This workshop will focus on a number of questions at this interface, including: (i) what does it mean for an immune repertoire to be "well-adapted", (ii) how can the actual dynamics of the adaptive system reach such a well-adapted state?, (iii) how should, and how does, the adaptive system react to an evolving pathogenic environment, and (iv) what are the molecular signatures of coevolution between viruses and the immune system, and how can we detect those from the biological data? This workshop will bring together many of the leading experts on these topics.