Jillyn Tittle
Ph.D. Student
Dr. John D. (Nick) Fisk's Lab
Department of Integrative Biology
When: Wednesday, April 23rd, 2025, 2:00pm - 3:30pm
Where: Student Commons (ACAD), Room 2504
Modeling the Molecular Dynamics of Engineered Filamentous Phage Systems for Phage Display Applications
Bacteriophages, viruses that infect bacteria, are the most abundant organisms on the planet. Bacteriophages, phages, are present in all ecological niches where their hosts are found and play an integral role in ecosystem maintenance. In the 100 years since the discovery of bacteriophages, they have become valuable tools for elucidating molecular biology in medicine, biotechnology, and material science, and their applications continue to expand. Our laboratory has developed a computational model to comprehensively simulate the lifecycle of M13, a single-stranded DNA (ssDNA) phage that infects E. coli. A major motivation for the construction of our model is that M13 is the original phage used for phage display. Phage display is prominent in molecular evolution technology where bacteriophages are genetically modified to display either peptide or protein libraries on the exterior of phage particles. A library of modified phage particles can be used to select specific binding molecules by exposing the library to a target molecule. Phage display was developed in 1985 by George P. Smith and used to evolve antibody drugs by Sir Gregory P. Winter, both of whom were awarded part of the 2018 Nobel Prize in Chemistry for their work.
My goal in this project is to expand the capabilities of the existing model of the natural M13 bacteriophage to describe biotechnological systems used for phage display and to provide a step towards modeling thousands of recently identified filamentous phages integrated into bacterial genomes. Objective 1. Analyze the dynamics in biotechnologically employed M13K07 helper phage that contains a second origin of DNA replication, p15A, in addition to a natural phage-based replication system. Objective 2. Simulate phage display systems that employ a second plasmid, a phagemid, that competes with the helper phage in order to produce decorated phage particles and package its genome. Objective 3. Explore how to generalize the native M13 phage model to CTXφ and other filamentous phages, most prominently through the addition of a genome integration module to the model.