PhD Discussion: Ángela Martínez-Mateos and Alice Perucca
Friday, May 16 @ 10:00 am–11:00 am
DnaA as a key regulator of ribonucleotide reductase genes in P. aeruginosa.
Ángela Martínez-Mateos, Bacterial Infections and Antimicrobial Therapies Group
Pseudomonas aeruginosa is a highly adaptable opportunistic pathogen that exhibits both acquired and innate antibiotic resistance mechanisms. Due to its survival capabilities in various environments, discovering new therapeutic strategies is essential. Ribonucleotide reductases (RNRs), essential enzymes for dNTP synthesis, have become promising targets for fighting P. aeruginosa infections. There are three main RNR classes (I, II, III), each distinguished by how their radical is generated, the metal required, cofactor type, structure, and oxygen needs. P. aeruginosa encodes all three RNR classes in its genome and understanding them is crucial for comprehending its metabolic adaptability under different growth conditions, such as planktonic, during infection, or biofilm formation.
Our laboratory previously discovered that class Ia (nrdAB) is regulated by AlgR, a positive transcriptional regulator that controls mucoidy in P. aeruginosa, and by NrdR, the master negative regulator of RNR that regulates all three classes. However, significant gaps remain in our understanding of the regulatory network of the class Ia RNR, and we don’t fully understand which transcriptional regulators are involved in the fine-tuning of gene regulation for the different RNR classes.
This project aims to identify new transcriptional regulators through genomic, transcriptomic, and proteomic approaches. It has been suggested that DnaA, among other transcriptional regulators, could be involved in the regulation of these pathways. Comprehensive studies of these regulators are necessary to elucidate the complex regulatory networks and hierarchical organization of these factors. Understanding these interactions is crucial for developing effective strategies to combat P. aeruginosa infections
Engineering the tumour ecosystem on a chip: a new tool to test cancer immunotherapies
Alice Perucca, Integrative Cell and Tissue Dynamics group
Immunotherapy has emerged as a revolutionary approach in cancer treatment, offering the potential for durable responses and improved patient survival. However, a significant proportion of patients fail to respond to these therapies, highlighting the need for a deeper understanding of the factors that govern treatment success. The tumour microenvironment, a complex ecosystem comprising various cell types and extracellular components, plays a critical role in shaping anti-tumour immune responses and influencing immunotherapy efficacy. Understanding the intricate interplay between tumour cells, stromal components, and immune cells within this microenvironment is essential for identifying the mechanisms underlying treatment resistance and developing strategies to overcome it. This project focuses on the development of a novel microfluidic “cancer-on-chip” device, a promising approach to model and study these intricated interactions in vitro. The device recapitulates key aspects of the tumour microenvironment, including spatial organization and cellular interactions, including cells of the immune system. By recreating an in vivo-like environment, this platform provides insights into immune cell behaviour in the tumour ecosystem and facilitates the screening of novel immunotherapeutic strategies.
