Plenary Lecture Ⅰ

Prof. Shuichi Takayama

Georgia Institute of Technology

USA

H-index=81 Organoid, Cellchip, Organic chemistry

TIME: September 29 (Thursday), 2022, 09:10-09:50

Background

Prof. Shuichi Takayama’s research interests started with bioorganic synthesis at the University of Tokyo and Scripps Research Institute. Subsequently he pursued postdoctoral studies in bioengineered microsystems at Harvard University as a Leukemia and Lymphoma Society Fellow. He spent 17 years at the University of Michigan in the Biomedical Engineering Department and Macromolecular Science and Engineering Program, then moved to the Wallace H. Coulter Department of Biomedical Engineering at the Georgia Institute of Technology and Emory School of Medicine in the summer of 2017. He is an associate editor of Integrative Biology and recipient of the Pioneers of Miniaturization Prize. He is also the Director of the Nakatani RIES Program which promotes international undergraduate student internships between the US and Japan.

Presentation

High-Throughput 3D MicroPhysiological Systems

This presentation will describe development of high-throughput (96 and 384 well format) 3D microculture models of the lung, renal proximal tubules, and breast cancer. The presentation will describe some of the underlying engineering technologies and materials science of the platforms along with accompanying biomedical applications of the technologies.

Specific engineering topics to be discussed include

1. Scaffold-free spheroid culture, scaffold-rich organoid culture, and a recently developed method of minimal Matrigel scaffolding approach to production of geometrically-inverted organoids in 384 hanging drop and ultra low attachment (ULA) plates.

2. Another topic will be development of a Transwell-96-based air-blood barrier array for study of lung infection and injury. Here, a buoyancy-mediated cell seeding enables convenient seeding of both sides of a Transwell insert. Air-liquid interface (ALI) culture is performed on the underside to facilitate convenient and rapid exposure of the epithelium to virus and then return back to ALI culture.

3. A final topic will be use of aqueous two-phase system (ATPS) bioprinting of micro-scars and observing the multiple steps of wound healing in vitro of clot formation, clot dissolution, collagen deposition, and wound contraction. These engineered models are used processes involved in study gut-bacteria interaction, breast cancer invasion, kidney injury, lung infection/injury and idiopathic pulmonary fibrosis (IPF).

Plenary Lecture II

Prof. Jinwon Lee

Sogang University, Seoul

Korea

Industrial biochemistry, Bioenergy, Marine Biotechnology, Metabolic and Systems Biotechnology

TIME: September 29 (Thursday), 2022, 15:00-15:40

Background

Prof. Jinwon Lee is the director of “C1 gas refinery R&D center (CGRC)” since September, 2015. CGRC is one of the biggest research centers funded by Ministry of Science and ICT, Korea and aims to develop catalysts and processes for converting C1 gas, especially methane and carbon monoxide (C1 meaning one carbon chemical), to more valuable chemicals.
Prof. Lee has received BS and MS degree at Department of Chemical Engineering, Seoul National University in 1987 and 1989, respectively. After moving to the United States, he continued to study biochemical processes at Department of Chemical Engineering, Carnegie Mellon University and got PhD degree in 1993.
Prof. Lee became a professor at Department of Chemical Engineering, Kwangwoon University in Korea in 1994. Since 2005, he has been working at Department of Chemical and Biomolecular Engineering, Sogang University.
Prof. Lee’s main research area is metabolic engineering and he has performed many studies for developing new biological catalysts by applying genetic techniques and modeling tools applicable to industrial fields. First concern was environment application of genetically adapted microbes to treat industrial pollutant, so called “bioremediation.”
Then he moved to industrial biotechnology (white biotechnology) to explore the possibility of substituting petroleum products by biological chemicals. Industrial biotechnology is environment-friendly and possible to prepare sustainable development for petroleum post era. By persuading Ministry of Trade, Industry and Energy with colleagues, it was decided to invest US $70 million (included US $40 million by private companies) on constructing demo plant (300 ton per year) for producing biochemical products. Currently, GS-Caltex company is known to commercialize more than 40 types of cosmetics containing 2,3-butanediol produced by developed biological process.
At the beginning of 2012, Prof. Lee was requested to design a new project for innovative technologies necessary for further economic growth from Ministry of Science and ICT, Korea. After successful planning of “C1 gas conversion agenda”, it was decided that US $125 million will be invested for developing essential catalysts and processes by establishing national-wide research center, named CGRC. Since 2015, Prof. Lee is the director of CGRC and successfully manages tens of research groups and projects.

Presentation

Challenges to develop technology for biological conversion of methane or carbon monoxide to useful chemicals

The potentials for reduction of major carbon emission of methane or carbon monoxide can be confirmed by introducing technologies and applications for bio-catalysts research groups of “C1 gas refinery R&D center (CGRC)”. First, we developed a platform methanotroph utilizing CH4 to produce valuable chemicals. Notwithstanding that methanotroph is the only nature-provided biocatalyst for sustainable production of chemicals from methane, the absence of genetic tools and the understanding of methanotrophic metabolism has obstructed further improvement. Herein, we achieved the methane-based biomanufacturers producing alcohols, organic acids, amines, olefine, biopolymer, isoprenoids, and biomaterials. In particular, polyhydroxyalkanoates (PHAs) have been produced in genetically engineered methanotrophs, and a commercial-scale process has been designed capable of producing 50,000 tons of PHB. The second is a CO hydration system that converts CO to formic acid, which consists of two key enzymes; CO dehydrogenase (CODH) and formate dehydrogenase (FDH). ChCODH-Ⅱ and MeFDH1 are highly active, however, they have fatal disadvantages of being vulnerable to oxygen and low-level expression, respectively. For successful biocatalytic process, developments of O2-tolerant ChCODH-Ⅱ with high EV-affinity and Me-FDHⅠ with high CO2 conversion preference were carried out by using structural analysis and enzyme engineering. As a result, formate was successfully produced from LDG without any pretreatment in a 100 mL fermenter and 10 L semi-pilot scale reactor. Each research result has proven that it is possible to efficiently control carbon emission from various emission sources, and the future demonstration plan and technology transfer strategy to industry are discussed.

Keywords

C1 gas refinery, Carbon-Neutral, Bio-catalyst, methanotroph, CO hydration

Plenary Lecture III

Prof. Ashutosh Chilkoti

Duke University

USA

H-index=103 Colorimetric biosensor, Drug Delivery

TIME: September 30 (Friday), 2022, 09:30-10:10

Background

Ashutosh Chilkoti is the Alan L. Kaganov Professor and of Biomedical Engineering at Duke University. His areas of research include genetically encoded materials and biointerface science. He has published ~330 papers, has been cited ~42,000 times, has a Google Scholar H-index of 107, and has 40 patents and 60 patent applications in process. Prof. Chilkoti was awarded the Clemson Award for Contributions to the Literature by the Society for Biomaterials in 2011, the Robert A. Pritzker Distinguished Lecture award by the Biomedical Engineering Society in 2013, was elected to the National Academy of Inventors in 2014, received the Distinguished Alumni award from the Indian Institute of Technology, Delhi in 2015, and the Diamond award from the College of Engineering at the University of Washington in 2017. He is a fellow of the American Association for the Advancement of Science. He is the founder of six start-up companies: (1) PhaseBio Pharmaceuticals, a publicly traded company on NASDAQ (sticker: PHAS) that is taking drug delivery technology that he developed into clinical trials; (2) Sentilus, a clinical diagnostics company that was acquired by Immucor in 2014; (3) BioStealth, a spinoff of Sentilus; (4) GatewayBio, that is commercializing a next-generation PEGylation technology for biologics; (5) Isolere Bio that is developing a non-chromatographic technology for purification of biologics; and (6) inSoma Bio that is developing a recombinant protein matrix for tissue reconstruction.

Presentation

A Next Generation PEG-like Polymer has Better Performance than PEG for Diagnostics and Drug Delivery

This talk will highlight recent work from my laboratory that illustrates the utility of a next generation “stealth” polymer whose lack of interaction with proteins and cells makes it useful for applications in clinical diagnostics and drug delivery. I will begin by describing the in situ synthesis of nanometer thick brushes of poly(oligo ethylene glycol methacrylate) (POEGMA) by surface-initiated polymerization. These nanometer thick brushes of POEGMA are “non-fouling”—they show extraordinary resistance to protein adsorption and the adhesion of cells. In the first application of POEGMA that I will discuss in this talk, a surface modified with a POEGMA brush provides the core—enabling—technology for a new point-of-care diagnostic—the D4 assay—that we have developed, in which all reagents are inkjet printed and stored on a ~30-100 nm thick polymer brush. The D4 assay is easy and cheap to manufacture, is multiplexable, provides quantitative results, and does not need a cold-chain for transportation or storage. In the second example of the utility of POEGMA, I will focus on its application in drug delivery. PEGylation—the covalent conjugation of biologic drugs with poly(ethylene glycol) (PEG)—is widely used to increase the circulation half-life and reduce the immunogenicity of biologic drugs, such as peptides, proteins, and aptamers. Although PEG has been touted as an inert and biocompatible material, recent studies have shown that PEG itself is immunogenic. Current estimates suggest that ~70% of the population has pre-existing antibodies to PEG, likely caused by chronic exposure to PEG. Anti-PEG antibodies can also lead to accelerated clearance and decrease the clinical efficacy of PEGylated drugs, while also increasing the risk and severity of allergic reactions to these drugs.
Conjugation of biologic drugs to POEGMA—which breaks up the long PEG chain into short oligomers that are appended as a side-chain to the polymer backbone— provides the same drug delivery advantages of traditional PEG conjugates, while simultaneously eliminating anti-PEG antigenicity. I will discuss its conjugation to three different types of biologic drugs: Exendin—a peptide drug for treatment of type 2 diabetes, uricase—a protein drug for refractory gout, and an aptamer drug to prevent clotting. Our studies show that: (1) POEGMA conjugates have better efficacy than the PEGylated version, (2) do not bind pre-existing PEG antibodies, (3) and do not themselves elicit antibodies against POEGMA. Collectively, these suggest that POEGMA is an attractive alternative to PEG for drug delivery.

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