UCLA iGEM

Both the mammalian immune system's complex defenses and a bacteriophage's targeting mechanism depend upon protein diversification. These models have inspired innovations ranging from targeted drug delivery to protein display. Using the major tropism determining (MTD) protein expressed on the Bordatella bacteriophage BPP-1, we aim to develop an in vitro system for generating antibody-like proteins that bind specified targets. The MTD protein expressed at the phage's tail fiber is naturally modified at its variable region to produce nearly 10¹³ possible binding variants while preserving its structure. Mutating the MTD's variable region by PCR can match the massive diversity of MTD in vitro. A library of MTD protein-DNA fusions generated by mRNA display can then be screened for binding against specified protein targets. This in vitro analog to phage display and immune clonal selection can be a powerful tool for constructing target-binding MTD variants with equally many varied applications.