Jhonatan Salgado-GarduñoPhD StudentEmail: j.salgado-garduno@qmul.ac.ukProfileProfileProject Title: Decoding Antibiotic Resistance: Cell Death, Phenotypic Responses, and Cell Wall Dynamics Summary: My research will explore the intricate interplay between antibiotics and bacterial behaviour. The primary focus is on understanding the impact of antibiotics on bacterial growth, cell shape, and biomechanics, with an overarching goal to develop a comprehensive quantitative understanding of how antibiotics influence bacterial shape and size, emphasizing the physical principles underlying deadly bacterial cell lysis. The project is structured across multiple stages. The initial phase seeks to unravel growth rate modulation in response to diverse media compositions and antibiotic concentrations, providing a pivotal foundation for the comprehensive investigation. Subsequently, an in-depth analysis of peptidoglycan synthesis using advanced tools such as Fluorescent d-Amino Acids, including HADA, will be carried out. Exploring mechanical properties and envelope architecture would lead to investigating changes under antibiotic stress, elucidating the molecular mechanisms controlling bacterial cell shape and size. Live cell imaging and machine learning-based image analysis techniques will be employed to explore bacterial cell-shape transformations under varying antibiotic concentrations. Extracted data will then be integrated into mathematical models and large-scale molecular dynamics simulations, advancing our understanding of the physical principles governing deadly bacterial cell lysis. The project not only contributes to a quantitative and physical understanding of bacterial cell death mechanisms but also proposes potential strategies for combination therapies. Through the simultaneous application of different classes of antibiotics, the goal is to effectively combat pathogenic bacteria and mitigate the emergence of antibiotic resistance. This research contributes to a broader understanding of antibiotic resistance and paves the way for innovative approaches to combat bacterial infections. Supervisor: Dr Nikola Ojkic Research