Revealing cell wall homeostasis mechanisms by interrogating the architecture of Streptococcus pneumoniae peptidoglycan with unprecedented resolution using AFM and STORMforce

Streptococcus pneumoniae is the leading cause of deaths by pneumonia (~ 1M people annually) and is becoming resistant to antimicrobials. We urgently require emerging solutions. However, we need to understand the basic principles that underpin bacterial cell life. Peptidoglycan, a component of cell wall, is the target for crucial antibiotics like penicillin but we lack understanding of its architecture, synthesis and how this is undermined by antibiotics. My ground-breaking research in Atomic Force Microscopy (AFM) has opened a whole new approach for investigating the cell wall. In this fellowship, correlating AFM with Stochastic Optical Reconstruction Microscopy (STORM), STORMforce, I will produce quantitative images of peptidoglycan molecular architecture. Combining cutting-edge microscopies and developing image analysis software, I will answer the following questions: - What is the peptidoglycan architecture of S. pneumoniae at ultra-resolution? - How does different enzymes activity influence the peptidoglycan architecture and its growth over time? - How does this dynamic macromolecule behave when antibiotics are present? This fellowship will launch my independent career and consolidate my leadership and project management skills. This will allow me to pursue my research interests and develop a key biophysical technique for the community (STORMforce in combination with software tools) that will answer pressing biological questions.