(3ii) Cellular engineering for sustainable bioenergy production and development of cellular therapies

Research Interests

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 with publications in JACS and Metabolic Engineering.

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 gut and skin microbiome. Through a just-in-time release mechanism, genetically engineered probiotics will release therapeutics only at the disease site and only when sufficiently accumulated.

Diversity and teaching Interests

As a former refugee from the Iran-Iraq war who has lived in many places in North America, I have personally felt the difference in environments where diversity is appreciated. Scientific challenges require a multidisciplinary, collaborative approach to leverage the unique perspectives of scientists from different fields. In the same manner, scientists from different ethnicities, gender, age, religion, sexual orientation and socioeconomic status also provide novel approaches and ideas. Therefore, an emphasis in diversity in the long-term will produce superior scientific results while also helping all of our communities.

I have a deep appreciation for the central goal of educating students in 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 develop a unique course in synthetic biology that is rooted in engineering applications.

Selected Publications (25 total, 14 first-author, 1 corresponding)

1. Amin Zargar, L Valencia, J Wang, R Lal, S Chang,M Werts, A Wong, V Benites, E Baidoo, LW Katz, JD Keasling, "A bimodular PKS platform that expands the biological design space", (Metabolic Engineering, 2020)
2. Amin Zargar, R Lal, J Wang, T Backman, P Cruz-Morales, AK Kothari, M Werts, A Wong, CB Bailey, A Loubat, Y Liu, V Benites, S Chang, AC Hernandez, JF Barajas, M Thompson, C Barcelos, R Anayah, H Garcia-Martin, A Mukhopadhyay, E Baidoo, LW Katz, JD Keasling, "Chemoinformatic guided engineering of polyketide synthases", (Journal of American Chemical society, 2020)
3. 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
4. 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)
5. 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.
6. Amin Zargar, DN Quan, KK Carter, M Guo, HO Sintim, GF Payne, WE Bentley, ‘Bacterial secretions of nonpathogenic coli elicit inflammatory pathways: a closer investigation of interkingdom signaling”, mBio (2015). 6:2 e00025-15.