CryoCLEMAV · Cryo-CLEM in situ imaging of adenovirus stepwise disassembly

Adenoviruses (AdVs) are very contagious viruses widespread in vertebrated. Human AdVs infections mainly affect children and immune-supressed people. On the other hand, AdV-derived vectors, nanocarriers and vaccines have turn out to be efficient therapeutic tools. Understanding AdVs disassembly mechanisms is vital to advance research in antiviral drugs, gene therapies, nanocarriers and vaccines. AdV particles’ metastability is key for surviving environmental conditions and cell defences, but at the same time, these particles should disassemble at the appropriate time and place during virus entry. The particle size and the speed of the process challenges the visualization of these events inside the cell. CryoCLEMAV aims at providing unprecedented structural insight on the process of virus entry and disassembly by combining virology with the cutting-edge microscopy techniques: correlative light and electron microscopy (cryo-CLEM), cryo-electron tomography (cryo-ET), FIB-milling and subtomogram averaging. This approach will allow to recapitulate the process with a previously unreachable resolution and specificity in a near native context of the host cell. CryoCLEMAV is an ambitious project whose success will be firmly supported by merging my expertise in virology and super resolution microscopy with the host lab knowledge and resources in cryo-EM techniques and adenovirus biology. Outcomes of this project will contribute to the development of several cryo-electron microscopy techniques and to the field of adenovirus biology, also impacting in the expanding field of adenovirus-derived therapeutic tools. All together will advance the research work of my host group, benefit the host organization (CNB-CSIC), and boost my professional career.