(6kq) Genetically Engineered Probiotics Designed at the Interconnect of Synthetic Biology and Metabolic Engineering

My proposed research platform will focus on three areas: 1) developing new genetic tools for cellular communication in prokaryotes and eukaryotes; 2) establishing new hosts for the production of bioactive compounds and 3) unifying my investigations in dynamic regulation and natural product synthesis towards the application of genetically engineered probiotics to treat gastrointestinal diseases.

During my PhD, I established a foundation in synthetic biology, a rapidly advancing discipline that impacts many aspects of society. With my background in mathematical modeling during my MS in chemical engineering, I sought to bring engineering rigor to my studies in cellular communication under the guidance of Dr. William Bentley. I elucidated the mechanisms in intra- and interkingdom communication systems and leveraged this understanding to genetically engineer bacteria for bioengineering and biomedical applications.

As a postdoctoral scholar in Dr. Jay Keasling’s laboratory, I have learned to design and manipulate the enzymes and pathways that lead to high-value products. I was awarded the NIH F32 National Research Service Award (NRSA) fellowship to develop an in-depth expertise in polyketide synthases (PKSs), a modular assembly-like enzyme that is responsible for the production of many pharmaceutical drugs. Informed by phylogeny and based in chemoinformatics, my work has advanced a new paradigm in manipulating these enzymatic pathways, and we have applied this knowledge to programmatically produce high-value chemicals in Streptomyces albus.

By marrying my graduate school expertise of dynamic regulation with my knowledge in metabolic pathways, I am developing a generalizable platform to produce disease-fighting molecules in the gastrointestinal system. Through a just-in-time release mechanism, genetically engineered probiotics will release therapeutics only at the disease site and only when sufficiently accumulated. I submitted an NIH K99 Transition to Independence application as a therapy to treat colon cancer, which would represent a vertical advance in cancer probiotic therapy.

Teaching Interests

As the product of universities that excel in both education and research, I have a deep appreciation for the role these twin aims in the mission of academia. My experiences together as a student and educator have helped me develop a teaching style that has been efficient and effective in both the classroom and laboratory. My basic educational beliefs can be distilled down to two distinct goals: (1) to inspire students and convey the fundamental and eventually more specialized aspects of science and engineering; and (2) to prepare students for a successful career that fosters independent thinking, ingenuity and effective implementation of the scientific process.

My diverse background in chemical and biomolecular engineering enables me to explain concepts and provide context in a multidisciplinary manner to retain the interest of diverse audiences. I am comfortable teaching undergraduate courses in traditional chemical engineering topics such as chemical kinetics and thermodynamics. and in bioengineering courses such as biofluids and genetic circuits. My foundation in these broad topics will allow me to provide a unique perspective on education in this interdisciplinary field.

Selected Publications (22 total, 12 first-author, 1 corresponding)

1. Amin Zargar*, S Chang, AK Kothari, AM Snijders, JHua Mao, T Bivona, JD Keasling, "Overcoming the challenges of cancer drug resistance through bacterial-mediated therapy", (Chronic Diseases and Translational Medicine, submitted) *Corresponding author
2. Amin Zargar, JF Barajas, R Lal, JD Keasling. "Polyketide synthases as a platform for chemical product design", AICHE Journal, (2018
3. Jesus Barajas, A Zargar, B Pang, V Benites, J Gin, E Baidoo, C Petzhold, N Hillson, JD Keasling, “Biochemical Characterization of b-Amino Acid Incorporation in Fluvirucin B2 Biosynthesis”, ChemBioChem (2018).
4. Amin Zargar, DN Quan, N Abutaleb, E Choi, WE Bentley, “Biocompatible capsules to control quorum sensing”, Biotechnology & Bioengineering (2016)
5. Amin Zargar, DN Quan, WE Bentley, “Reducing stochasticity in cell populations: rewiring quorum sensing to engineer dynamic gene expression with population-level control”, ACS Synthetic Biology (2016)
6. Amin Zargar, DN Quan, M Emamian, CY Tsao, HC Wu, CR Virgile, WE Bentley, “Rational design of ‘controller cells’ to manipulate protein and phenotype expression”, Metabolic Engineering (2015). 30: p. 61-68.
7. Amin Zargar, DN Quan, KK Carter, M Guo, HO Sintim, GF Payne, WE Bentley, ‘Bacterial secretions of nonpathogenic E. coli elicit inflammatory pathways: a closer investigation of interkingdom signaling”, mBio (2015). 6:2 e00025-15.