Research Topics

A. Dynamic modulation of cellular phenotypes

In nature, dynamic interactions between proteins play a crucial role in defining many cellular functions such as metabolism, cell signaling, transcription regulation, apoptosis, cellular targeting, and protein degradation. By controlling the spatial and temporal organization of these supramolecular complexes, cellular functions can be modulated in a highly dynamic manner for optimum efficiency. Understanding how these proteins interact holds the key to deciphering their roles in native cellular function and in creating new cellular functions for synthetic biology applications. By adding logical components into our designs, our goal is to create new synthetic biology frameworks that are dynamic in nature in order to adapt to the constantly changing cellular environments for dynamic modulation of phenotypes on demand.

  • Project 1. Synthetic Control of Metabolism by Dynamic Metabolons (NSF)

    Project 1. Synthetic Control of Metabolism by Dynamic Metabolons (NSF)

    The ability to optimize pathway flux is one of the most important factors toward maximizing product titers. The traditional approaches largely focused on the overexpression of rate-limiting enzymes, competing pathway deletion, and resource management. However, most of these approaches are static in nature and do not provide dynamic regulation of pathway fluxes based on substrate,…Continue…

  • Project 2. Repurposing the CRISPR-Cas9 system for dynamic control of cellular metabolism (NSF) – with Prof. Papoutsakis

    Project 2. Repurposing the CRISPR-Cas9 system for dynamic control of cellular metabolism (NSF) – with Prof. Papoutsakis

    Cellular metabolism is capable of highly specific and efficient chemical synthesis at mild temperatures and pressures far beyond the capability of most synthetic chemical routes. Although pathway engineering can be used to further improve the range of compounds that could be synthesized, achieving commercially viable productivity remains challenging. An emerging strategy to combat these issues…Continue…

  • Project 3. Redirecting cellular metabolism via synthetic toehold-gated dCas9 regulators (NSF)

    Project 3. Redirecting cellular metabolism via synthetic toehold-gated dCas9 regulators (NSF)

    Cellular metabolism is capable of highly specific and efficient chemical synthesis at mild temperatures and pressures far beyond the capability of most synthetic chemical routes. Engineering specific pathways can be used to further improve the range of compounds that can be synthesized but it is a major challenge to achieve commercially viable productivity. To maximize…Continue…

  • Project 4. Dynamic modulation of cellular functions by controlled protein degradation (NSF)

    Project 4. Dynamic modulation of cellular functions by controlled protein degradation (NSF)

    Aberrant protein levels and activities contribute to numerous diseases, including cancers, cardiovascular disease, diabetes, and neurodegenerative diseases. No current therapy dynamically degrades excess protein(s) to treat diseases. The ability to tightly coordinate the levels of cellular proteins is critical for normal healthy cells to maintain homeostasis. We are developing new strategies that elicit dynamic and…Continue…

B. Nano protein scaffolds for biocatalysis, biosensing, and therapeutics

Proteins are the most versatile among the various biological building blocks and efforts in protein engineering have resulted in many industrial and biomedical applications. Our approach is to exploit the modular nature of different protein domains in order to design synthetic protein scaffolds that can perform completely new biological functions. We are developing new strategies in designing exchangeable protein domains for predicative engineering applications in (1) biocatalysis, (2) biosensing, and (3) disease therapeutics.