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Bacterial cell envelopes include a cell wall made of peptidoglycan, a cross-linked polymer network that provides most of the load-bearing structure that maintains cellular integrity. Understanding how the wall performs this role under the competing demands of cell growth and division, how it fails under the action of wall targeting antibiotics, and how it is altered in antimicrobial resistant organisms, is an ongoing subject of study. Atomic force microscopy (AFM) provides a unique capability for imaging cell wall architecture down to the molecular scale in the native hydrated state, overturning common textbook representations of the wall as an ordered “lattice” in Gram positive bacteria¹. Under the action of cell-wall targeting antibiotics, such as the beta-lactams, we find that cell death of the important pathogen Staphylococcus aureus is driven by the upset of wall homeostasis, with peptidoglycan hydrolysis continuing in the absence of synthesis leading to wall spanning holes and ultimately death². Similar studies on the Gram-negative pathogen E. coli, where the molecular 2-d material of the wall provides an opportunity to explore failure mechanisms at unprecedented resolution, will also be described.

Expanding this work to antimicrobial resistance, we find that in MRSA high level resistance is the result of two co-dependent mechanisms, one enabling continued cell wall synthesis of the large majority of the cell wall peptidoglycan, and the other, resulting from mutation in RNA polymerase induced physiological changes, allowing the cell to divide without a usually critically important component of the cell wall architecture³. Finally, we will discuss how broadening our AFM based approach to study cell walls in other kingdoms of life (fungi and plants), can provide new insights into how similar structures have evolved to solve the same physical challenges of maintaining mechanical integrity while allowing growth and division, despite utilising very different polymer chemistry.  

1. Pasquina Lemonche et al, Nature, 582, 294-297 (2020)
2. Salamaga et al, PNAS, 118, e2106022118 (2021)
3. Adedeji-Olulana, Science, in press

15:15: Coffee Break

15:30: Johannes Mischo (B2, AG Jacobs): Cell wall age influences the adhesion capability of S. aureus

15:45: Ben Wieland, Dr. Gubesh Gunaratnam: (B2, AG Bischoff) Studying the biophysical aspects of pathogenic microbes on artificial and biotic surfaces (by SCFS)

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The ongoing battle against therapy resistance in antibiotic and cancer treatments remains one of the primary challenges in biomedicine. Densely packed cellular populations, such as microbial biofilms or solid tumors, seem to be particularly resilient.Understanding how physical mechanisms and spatial heterogeneities shape resistance evolution and treatment response in these actively proliferating granular matter systems is essential for the development of novel therapeutic strategies. Our research adopts an interdisciplinary approach that combines genetically engineered microbial and cancer cell in vitro systems with mathematical modeling, agent-based simulations, and machine learning. In my presentation, I will show how collective dynamics in dense cellular populations inherently enhance drug resistance evolution across complex fitness landscapes. I will then use this framework to demonstrate the transformative potential of reinforcement learning for artificial scientific discovery and adaptive therapy optimization. Finally, I will explore how these concepts could be extended to integrate components of immunotherapy. Together, these vignettes aim to demonstrate the power of integrating predictive physical models with data-driven research approaches to unravel —and potentially guide— the evolutionary dynamics in complex living systems.

15:15: Coffee Break

15:30: Enrique Colina  (A10, AG Lautenschläger): Pretubulysin, as a microtubule destabilizing agent. A computational insight to its binding mechanisms

15:45: Dr. Mariana Romeiro Motta (A13, AG Aradilla-Zapata): The role of MAP65-mediated microtubule nucleation in plant development

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