PhD defence

Using cryo-EM methods to uncover structure and function of bacteriophages

• R. Ouyang

Date

Tuesday 5 December 2023

Time

12:30 - 13:15 hour

Address

Academy Building
Rapenburg 73
2311 GJ Leiden

Supervisor(s)

• Prof.dr. A. Briegel
• Prof.dr. D. Claessen

Summary

Bacteriophages are the most prevalent biological entities, influencing bacterial evolution and communities. Their omnipresence and potential applications in medicine and industry make them vital for scientific exploration. This research delves into the molecular structure and function of two bacteriophages using cryo-electron microscopy (cryo-EM) techniques, combined with advanced image processing and artificial intelligence. These phages possess flexible elements crucial for infection, posing challenges for structural studies.
In this research, the cryo-EM methods including single-particle analysis and cryo-electron tomography were employed to study bacteriophages with flexible fibers. To obtain a comprehensive understanding of the structure and function of these phages, a combined research approach was adopted, integrating sequence prediction, protein structure prediction, computational simulation, and machine learning algorithms. Moreover, a protocol for processing single-particle analysis data was developed to balance result quality and computational resources. Additionally, an efficient neural network algorithm was used to automatically extract complex fiber structures from cryo-electron tomography data.
Specifically, we studied about a jumbo bacteriophage infecting Klebsiella pneumoniae strains and a flagellotrophic phage infecting Agrobacterium emphasizing the significance of examining tail and capsid fibers in various phages, revealing their potential to offer insights into phage infection mechanisms.
Advancements in computer technology and electron microscopy have broadened research horizons, allowing in-depth studies of proteins and biological macromolecular machines. This research offers insights into phages with flexible components, presenting a beneficial workflow for similar research endeavors.

PhD dissertations

Approximately one week after the defence, PhD dissertations by Leiden PhD students are available digitally through the Leiden Repository, that offers free access to these PhD dissertations. Please note that in some cases a dissertation may be under embargo temporarily and access to its full-text version will only be granted later.

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