Engineering nanoscale protein containers
Abstract
Synthetic biology is a growing field with great potential for the development of microbes or even artificial cells to produce chemicals and materials on demand from a variety of energy and nutrient sources. Several advances led to the commercialization of a malaria drug precursor and a commodity chemical used to make fibers, but there are limits to the available methods used to push forward the field, particularly with respect to the complexity of cellular reactions and the need for segregation of some reactions. The work proposed here will enable the design of in vivo and in vitro protein containers that assemble to encapsulate cargo from engineered metabolic pathways to toxic materials, and could eventually be applied to uses such as drug delivery, nanomaterial fabrication, and biosensing. The starting point is a bacterial microcompartment, or ÔorganelleÕ found natively in bacteria. Despite much work on several native microcompartment systems in recent years, challenges remain that currently prevent their widespread use in these applications. Notably, the rules governing the assembly of the structures within the cell are not well understood, and to date there are no reports of compartment assembly outside of the cellular context. Moreover, the process of cargo encapsulation in these containers is not well understood, especially in terms of loading and stoichiometry for more than one target molecule simultaneously. The objectives of this work are to identify the requirements for proper microcompartment formation both in bacteria and in cell-free (in vitro) environments, and to control the cargo loading into these microcompartments. Together, these studies will enhance our understanding of natural systems involved in the microbial world, including the human gut microbiome, while establishing guidelines for the design and loading of these structures for a variety of potentially transformative applications.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jun 03, 2019
- Source ID
- W911NF1610169
Entities
People
- Danielle Ercek
Organizations
- Army Contracting Command
- Northwestern University
- United States Army