RT Dissertation/Thesis
T1 Monitoring the evolution of drug targets of pathogens to improve the design of therapies
T2 Monitorizando la evolución de dianas terapéuticas de patógenos para mejorar el diseño de terapias
A1 Ferreiro Garcia, David
K1 2409.03 Genética de Poblaciones
AB Some diseases caused by intra-host pathogens (such as viruses or bacteria) are generally treated by pharmacological therapies designed, among other aspects, from an evaluation of the  pharmacological targets observed at a given time. Thismethodology ignores the processes of population genetics and molecular evolution occurring in the pathogen. However, pathogen populations evolve, often leading to the emergence of drug resistance and, consequently, to the need for designing and applying a new therapy. Therefore, therapies that consider the past and future evolution of pathogens, and their molecular targets, are expected to be active for longer than therapies based on traditional methods. In this doctorate we aim todevelop and apply evolutionary strategies to improve the design of pathogen therapies. These strategies include (1) development of a computational method for the evolutionary analysis of molecular targets based on the approximate Bayesian computation approach, (2) inference of centralized proteins of pharmacological targets of pathogen populations, (3) analysis of the influence of drugs on the genetic diversity and molecular evolution of the pathogen, (4) identification of the influence of resistance mutations on the protein stability of drug targets and, (5) prediction of the evolution of protein drug targets and interpretation for the design of therapies. In summary, we aim to determine which evolutionary aspectsof protein drug targets are most important for the design of therapies.Methodologically, we will apply advanced models of evolution that consider substitution, recombination, selection and demography of pathogen populations. Despite in this project we will focus on HIV-1, the proposed methods could also beapplied to populations of other pathogens.
LK http://hdl.handle.net/11093/7260
UL http://hdl.handle.net/11093/7260
LA eng
NO Xunta de Galicia | Ref. ED481A-2020/192
DS Investigo
RD 07-oct-2024