(6jx) Application of Advanced Synthetic Biology Tools to Genetic Engineering and Bioprocessing | AIChE

(6jx) Application of Advanced Synthetic Biology Tools to Genetic Engineering and Bioprocessing


Cao, J. - Presenter, Massachusetts Institute of Technology
Research Interests:

I did my Ph.D. in Chemical Engineering with Prof. Ravi Kane in the Department of Chemical and Biological Engineering at Rensselaer Polytechnic Institute (RPI), where I developed optogenetic and synthetic biology tools for gene expression regulation. My research unites design principles of synthetic transcriptional systems and the mechanism of translation to invent new synthetic RNA systems. 1) I developed the first optogenetic system of controlling gene expression at translational level, based on the light-inducible reconstitution of a RNA binding domain and a translation initiation domain. 2) I have also invented a novel approach to control target mRNA translation using designable protein scaffolds (PUF domains) which enables either upregulating or downregulating the translation of a single mRNA. 3) To further extend this work, I utilized RNA binding domains to repress translation in a prokaryotic operon, enabling selectively regulating individual genes in a polycistronic mRNA, which cannot be achieved at the transcriptional level.

I am currently doing my postdoc work with Prof. Timothy Lu at Synthetic Biology Center at MIT, while co-mentored by Prof. Manolis Kellis at MIT Computer Science & Artificial Intelligence Laboratory (MIT CSAIL). My work focuses on the development of novel synthetic biology tools to disrupt disease diagnostics and drug manufacturing. I integrated synthetic biology and chemical engineering methods to establish a consolidated drug manufacturing platform of cell engineering, upstream and downstream bioprocessing for rapid, flexible and on-demand drug production. I developed a recombinase-based library screening method, which can be used to screen some difficult-to-screen libraries, and leverage machine learning to identify new 5’UTRs that can enhance protein expression in DNA vaccines and mRNA therapeutics. A MIT invention based on this work was licensed to Senti Bioscience, Inc.

Last year, I was awarded $100,000, as a recipient of the inaugural Shark Tank Grant, by Broad Institute of MIT and Harvard to develop a novel approach to detect rare mutations without prior knowledge of the locations for early cancer detection. In addition, I also applied cutting-edge NGS methods to mapping the single-cell epigenome, genome and transcriptome for multi-omics study of melanoma cells to discover new biomarkers for early diagnostics.

In the future, my lab will focus on the integration of synthetic biology, next-generation sequencing (NGS), single-cell technologies, genomics and artificial intelligence (AI) to develop AI-powered high-throughput profiling and screening strategies for drug target validation and lead optimization. In addition, I will adapt my flexible drug platform to cell-free gene expression systems, and develop new aptamer-based selective purification approach to produce high-quality biological drugs in a few hours at any location. I will also continue my liquid biopsy-based early cancer and Alzheimer’s disease detection work in collaboration with Kellis and other bioinformatics labs. I aim to advance precision medicine with an integrated platform of early disease detection, drug target discovery and lead optimization, and point-of-care drug manufacturing.

Teaching Interests:

I enjoy teaching and mentoring. I had served as a teaching assistant for Transport Phenomenon and Bioprocessing and Biochemical Engineering Lab classes when I was a graduate student at RPI. I was a lab liaison for Innovation Teams (i-Team) at MIT for worked with three students in Sloan School of Management to explore the opportunities of commercializing the technologies that I co-developed in the lab. I am excited to teach core courses such as Transport Phenomena, Separation Processes and Chemical Reaction Engineering, or bio-related courses or labs including Bioprocessing Engineering, Biochemical Engineering and Chromatography. I am also passionate to develop new courses on synthetic biology and genomics, or other industrial related topics such biomanufacturing and next-generation sequencing.

Selected Publications:

  1. Cao J*, Novoa EM*, Zhang Z, Kellis M, and Lu TK. High-throughput engineering of 5’-untranslated regions by machine learning-powered library design and recombinase-based library screening. (Manuscript in preparation; Provisional patent filed in June 2018) (* Equal contribution)
  2. Cao J, Perez-Pinera P, Lowenhaupt K, Wu M, Purcell O, Fuente-Nunez C, Lu TK, Versatile and on-demand biologics co-production in yeast. Nature Communications, 2018, 9, 77.
  3. Cao J*, Fuente-Nunez C*, Ou R, Torres M, Pande S, Sinskey AJ, Lu TK, Yeast-based synthetic biology platform for antimicrobial peptide production. ACS Synthetic Biology, 2018, 7, 896-902. (* Equal contribution)
  4. Cao J, Arha M, Sudrik C, Mukherjee A, Wu X, Kane RS, A universal strategy for regulating mRNA translation in prokaryotic and eukaryotic cells. Nucleic Acids Research, 2015, 43, 4353-4362.
  5. Cao J, Arha M, Sudrik C, Schaffer DV, Kane RS, Bidirectional regulation of mRNA translation in mammalian cells by using PUF domains. Angewandte Chemie International Edition, 2014, 126, 5000-5004. (Selected as a Hot Paper by the editors)
  6. Cao J, Arha M, Sudrik C, Bugaj L, Schaffer DV, Kane RS, Light-inducible activation of mRNA translation in mammalian cells. Chemical Communications, 2013, 49, 8338-8340.

Patents and Innovations:

  1. “Tools for Next Generation Komagataella (Pichia) Engineering.” Inventors: Lu TK, Perez-Pinera P, Cao J, Purcell O. US Patent Application No.: 62/360,731, International Patent Application No.: PCT/US2017/041509. Filed: July 11, 2017.
  2. "pVAX-TP901, pVAX-phiC31, pVAX-BxB1, pVAX-R4, pCAG-phiBT1-NLS_IRES_Zeo, pCAG-Wbeta-NLS_IRES_Zeo, pFUGW-BxbI-attP-EYFP-hygro, HEK-LP" Inventors: Lu TK, Cao J, and Barbara J. MIT Case No. 19018. This technology is licensed to Senti Bioscience, Inc.
  3. “High-Throughput Untranslated Region Engineering and Screening.” Inventors: Lu TK, Kellis M, Cao J, Novoa EM, and Zhang Z. U.S. Provisional Application No.: 62/685,421. Filing Date: June 15, 2018.