SynBioBeta 2023

Speaker Bio: Biao Lu, MD, PhD, is an Associate Professor in Bioengineering at Santa Clara University. He has published over 60 peer-reviewed manuscripts; 4 book chapters and 43 peer-reviewed conference proceeding papers, and 4 patents. His major discoveries in the field of nanoscale exosomes include: (1) invented exosome surface display technology using tetraspanins such as CD9, CD61, and CD81; (2) invented pseudotyping technology for genetic modification of exosomes in cultured human cells; (3) Genetic engineering strategies using human cell-derived exosomes for the treatment of inflammation and lysosomal storage diseases; and (4) currently working on exosome-based vaccination for viral infections and for the prevention and treatment of cancers.

Abstrac: Human cell-derived man-sized exosomes are the fast-growing class of biologics with huge potentials for the treatments of many human diseases such as hereditary and metabolic disorder, inflammation, viral infection and cancer. Native exosomes, however, usually do not carry therapeutics or lack the ability for disease-targeted delivery, therefore limiting their potentials for clinical translation. These functions can be introduced to exosomes either by genetic manipulation of living producer cells or alternatively by chemical modification after exosome isolation. Although genetically reprogramming of exosomes living cells is straightforward, the design and construction of highly complicated fusion genes appear to be challenging by using the conventional gene cloning technology. In this front, synthetic biology offers a robust solution for fast generation of fusion genes in any expression cassettes, therefore enabling the production of genetically engineered therapeutic exosomes in living human cells. This seminal talk focuses on synthetic biology and its application for exosome surface engineering for both the installation of targeting molecules on the outer surface and the therapeutic loading of protein therapeutics in the lumen. Furthermore, case studies on how exosomes are genetically engineered to produce exosome-based nanomedicine for the treatment of inflammation and lysosomal storage disease are also discussed.

Speaker Bio: Dr. Mark Blenner is an Associate Professor of Chemical & Biomolecular Engineering at the University of Delaware. Prior to that, he was the McQueen Quattlebaum Associate Professor of Chemical and Biomolecular Engineering at Clemson University. He received his PhD in Chemical Engineering from Columbia University in 2009 and completed three years of postdoctoral training as an American Heart Association Postdoctoral Fellow and an NIH NRSA Postdoctoral Fellow at Harvard Medical School and Children’s Hospital Boston. In addition to winning the 2022 AIChE Food, Pharmaceutical, and Bioengineering Early Career Award, he also won the 2022 Biochemical Engineering Journal Young Investigator Award, the 2021 ACS BIOT Young Investigator Award, the Presidential Early Career Award for Scientists and Engineers (PECASE), the 2020 South Carolina Governor’s Young Scientist Award for Excellence in Scientific Research, the 2019 Clemson University Junior Researcher of the Year, and several Young Faculty Awards from DARPA, NIH, NASA and the Air Force. His research is broadly focused on engineering biomolecular and cellular systems for the production of fuels, chemicals, enzymes, biopharmaceuticals and biosensors. Some of the common threads across his lab’s work are around using microbes for enabling a circular economy, and addressing biomanufacturing-related problems arising from cell line design.

Abstrac: Microorganisms have always been integral to natural circular processes in the environment. They serve an important role in converting complex biological molecules into central building blocks that can be converted back into complex products. As a society, we now seek similar circularity in the semi-synthetic world that we’ve constructed through over a century of synthetic organic chemistry. Recent advances in genomics and synthetic biology have enabled exploitation of a wide array of microbes engineered to produce value-added products from biomass-derived and synthetically derived substrates. Our group has mainly focused on oleaginous yeast – that use a variety of low-value and waste feedstocks and can naturally accumulate a large amount of lipids. We have engineered multiple genetic tools to rapidly engineer Yarrowia lipolytica, and used these tools to elucidate cryptic metabolic pathways, and to produce oleochemicals and secondary metabolites by taking advantage of naturally high flux pathways. We will also describe our work with emerging microbes that have more favorable properties for utilizing low-value and waste substrates, including lignin derived aromatics and plastic waste.

Speaker Bio: Dr. Possu Huang received his PhD from Caltech with the first demonstration of a computationally designed novel protein-protein interface. He subsequently conducted postdoctoral research at the University of Washington before starting his group at Stanford. His research focuses on advancing the understanding of proteins for the engineering of novel therapeutics and other protein-based nanotechnology. He has contributed to a large number of de novo designed proteins, most notably to the unlocking of the design principles behind the TIM barrel fold and the invention of eOD, an HIV immunogen design currently in clinical trials as a potential vaccine. His group uses machine learning, computational modeling, structural biology and experimental library optimization to continue the expansion of protein-based molecular platforms.

Abstrac: Major histocompatibility complexes (MHCs) play a central role in the immune response by allowing antigens to be presented on cell surface. This unique feature has inspired research efforts in developing methods to target MHCs as disease markers. T cells receptors (TCRs) are the natural receptors to MHC, but they are evolved to be low affinity and promiscuous. Engineering TCRs (or similarly structured antibody-based mimetics) to improve their stability and affinity for MHC is possible, but it generally requires laborious experimental efforts. We developed a biologically-inspired novel protein platform to enable the facile development of MHC binders: through a single variable loop, binders highly specific to a target antigen can be developed, to single-residue level discrimination. This new syn-bio solution to the critical challenge could vastly expand our ability in research, targeting, diagnosis and developing therapeutics.

Speaker Bio: Dr. Deepak Raghothaman is the Director of Business Development at Allozymes, and part of the management team since Jan 2022. He leads the global business strategy and customer partnerships for the service and product business. He brings over 10 years of experience in strategy and innovation in life sciences & Biotech. Prior to this, he had a double-hat with a Global CPG, leading APAC strategic innovation and business development in Biotech and Agrisciences. Deepak has a PhD in Biomedical sciences, and worked as lead scientist prior to his corporate role. He has 3 invention disclosures, 2 patent applications, and over 5 peer-reviewed scientific publications, including a spin-off that was acquired in 2019.

Abstrac: Allozymes is developing a proprietary next-gen synthetic biology platform by leveraging ultra-high throughput microfluidics for speed scaling novel industrial biosolutions. Our proprietary technology allows us to test enzymes and strains 1000x faster than advanced robotics. We run 10M experiments per day at fractional cost and increase the chance of success by 200x in developing industrially relevant enzymes and strains. We are on a mission to reduce 2 M tons of CO2 emission annually by replacing traditional manufacturing methods with cleaner, greener, scalable methods, by unlocking the power of custom-designed enzymes. Allozymes is playing a significant role in unlocking infinite possibilities through enzymatic development with the plan of having a database of custom enzymes for a variety of production lanes, reducing emissions substantially, and offering sustainable solutions across sectors to address the $1-2T market.