Caltech

Our Project

Our project attacks the following problem: can one engineer viruses to selectively kill or modify specific subpopulations of target cells, based on their RNA or protein expression profiles?

This addresses an important issue in gene therapy, where viruses engineered for fine target discrimination would selectively kill only those cells over- or under-expressing specific disease or cancer associated genes. Alternatively, these viruses could be used to discriminate between strains in a bacterial co-culture, allowing strain-specific modification or lysis.

This is clearly an ambitious goal, so we brainstormed a simple model of this problem suitable for undergraduates working over a summer. The bacteriophage λ is a classic, well studied virus capable of infecting E. coli, another classic model genetic sytem. We therefore seek to engineer a λ strain targeted to lyse specific subpopulations of E. coli based on their transcriptional profiles. Together, λ and E. coli provide a tractable genetic model for this larger problem, while hopefully providing lessons applicable to more ambitious, future projects.

For details on our design, please see our Project page. For a brief description of our results, see the Highlights page

About iGEM

Synthetic biology implies the modification of existing biological pathways or construction of new systems to perform useful tasks, as well as the development of foundational technologies to allow for the more reliable design of biological systems. Many major problems in the field stem from the perceived unreliable and variable nature of complex biological systems. Most biological systems exhibit inherent variations in system behavior. These variations, along with the current lack of understanding around organizing principles in biological systems, limit the ability to engineer reliable biological systems. If foundational technologies can be developed that allow for standardization, decoupling, and abstraction, synthetic biology will expand to an engineering discipline that will advance applications in many fields. If successful, engineers could design and construct new systems in relatively short periods of time using well-characterized parts.

The International Genetically Engineered Machine (iGEM) competition involves the design and implementation of a synthetic biological system. Construction requires combining newly constructed with an existing library of known parts in new ways to construct a novel system. The project has two goals: firstly to create an interesting device for iGEM, and secondly to determine the viability of using standardized parts. The Caltech iGEM project focuses on using viruses to selectively kiss host cells, with the viral decision resting on whether the host produces a correct riboregulator key.