Plenary Lecture I

Prof. Bernhard Palsson

Y.C. Fung Endowed Professor in Bioengineering, Professor of Pediatrics, UC San Diego

USA

H-index: 177 (record from Google Scholar)

Research

• Systems biology
• Data analytics
• Computational biology

Background

Bernhard Palsson is the Y.C. Fung Endowed Professor in Bioengineering, Professor of Pediatrics, and the Principal Investigator of the Systems Biology Research Group in the Department of Bioengineering at the University of California, San Diego. Dr. Palsson has co-authored more than 700 peer-reviewed research articles and has authored four textbooks, with more in preparation.

He is inventor on over 40 U.S. patents, the co-founder of several biotechnology companies, and holds several major biotechnology awards. He received his PhD in Chemical Engineering from the University of Wisconsin, Madison in 1984. Dr. Palsson is a member of the National Academy of Engineering and is a Fellow of the AIChE, AIMBE, AAAS, and the AAM. Dr. Palsson has been a Clarivate Highly Cited Researcher since 2014.

Presentation

What are iModulons?

The first microbial genome sequences appeared in the mid to late 1990s. In the 2000s, computational biology at the genome-scale arose through the reconstruction of metabolic networks based on functional gene annotation. In the late 2000s, the cost of DNA sequencing dropped massively, leading to rapidly expanding data bases of microbial genome sequences and microbial transcriptomes. These data sets could be knowledge-enriched and decomposed into coherently functioning sets of genes using machine learning methods. A growing number of data types can be processed in a similar fashion. Multiple data types can now be made interoperable based on known mechanisms and molecular functions. The 2020s are likely to see an accelerating fine-grained understanding of microbial physiology.

Analysis of large biological data sets can take place at four levels. At level 1 we perform multi-variate statistics, at level 2 knowledge-enrichment of large data sets, at level 3 systems biology and computational modeling, and at level 4 detailed biophysical modeling. Levels 1 and 4 are well developed in the literature. The history of genome-scale models, level 3, is about 20 years old with much progress made. Level 2 is the least developed and is focused on knowledge mapping and the use of machine learning and explanatory AI.

This talk will focus on progress at levels 2 with transcriptomes. Large compendia of high-quality RNAseq profiles can now be decomposed using Independent Component Analysis (ICA). ICA identifies independently modulated sets of genes, called iModulons. This talk will show the uses of iModulons for metabolic engineering and bioprocess development: including cross-species transfer of iModulons, Media composition, expression of heterologous genes, and y-gene discovery.

Plenary Lecture II

Prof. Hanjoong Jo

Wallace H. Coulter Distinguished Chair Professor in Biomedical Engineering, Associate Chair for Emory
Director of Cardiovascular Biomechanics T32 Program at Emory and Georgia Tech

USA

H-index: 84 (record from Google Scholar)

Research

• Vascular mechanobiology
• Endothelial mechanobiology
• Atherosclerosis
• AV disease
• Therapeutic

Background

Dr. Hanjoong Jo is Coulter Distinguished Chair Professor and Associate Chair in the Department of Biomedical Engineering (BME) and the Department of Medicine at Emory University and Georgia Tech, where he directs the Cardiovascular Mechanobiology, Therapeutics, and Nanomedicine Lab. He is the Director of the Cardiovascular Biomechanics T32 Graduate Training Program at Emory/GT. He studies how blood flow regulates vascular endothelial function, leading to atherosclerosis and aortic valve disease. He has trained >60 trainees, including PhDs and postdocs, many of whom have become successful members in universities, industries and government. He has published >240 peer-reviewed papers and written three books. He is an elected fellow of the AAAS, BME Society, Am Institute of Medical and Biomedical Engineers, Am Heart Association, and Am Physiological Society. He received a Marshall Distinguished Investigator Award from the British Society of Cardiovascular Research. He has served as an Editorial Board Member and Associate Editor of many high impact journals. He was the Chair of the 2012 Annual BME Society Meeting, the 2023 Gordon Research Conference in Biomechanics of Vascular Biology and Disease, and the International Symposium in Biomechanics in Cardiovascular Diseases. He was the Vice President of the Korean-Am Scientists and Engineers Association.

Presentation

Flow-Induced Reprogramming of Endothelial Cells (FIRE) in Atherosclerosis: From Mechanobiololgy to Mechanomedicine

Atherosclerosis is the major underlying cause of myocardial infarction and stroke. It occurs preferentially in arterial regions exposed to disturbed flow (d-flow) by mechanisms involving broad changes in the expression of genes. Using the partial carotid ligation model of atherosclerosis in mice and single cell OMICs studies, we revealed the roles of flow-sensitive genes in endothelial dysfunction and atherosclerosis. The single cell OMICs and validation studies revealed that d-flow reprograms endothelial cells to proatherogenic phenotypes, including inflammation, endothelial to mesenchymal transition (End-MT) and endothelial-to-immune cell-like transition (EndIT). The scRNAseq study revealed several novel flow-sensitive genes, such as HEG1 and how they regulate endothelial function and atherosclerosis. I will also discuss how we target those flow-sensitive genes to develop novel anti-atherogenic therapeutics and pursue endothelial-targeted delivery of therapeutics.

Plenary Lecture III

Prof. Hiroaki Suga

Professor at Department of Chemistry, Graduate School of Science, The University of Tokyo

Japan

Research

• Artificial ribozymes
• Genetic code reprogramming
• Ribosomal synthesis of nonstandard peptides
• nonstandard peptide probes

Background

Hiroaki Suga received Ph. D. in Chemistry (1994) from MIT. After three years of post-doctoral work in Massachusetts General Hospital, he became Assistant Professor in the Department of Chemistry in the State University of New York at Buffalo (1997) and promoted to the tenured Associate Professor (2002). In 2003, he moved to the Research Center for Advanced Science and Technology in the University of Tokyo. In 2010, he changed his affiliation to the Department of Chemistry, Graduate School of Science. He is the recipient of Akabori Memorial Award 2014, Japanese Peptide Society, Max-Bergmann Gold Medal 2016, Vincent du Vigneaud Award 2019, The Research Award of the Alexander von Humboldt Foundation 2020, MIT T.Y. Shen Lectureship 2022, ETHZ Prelog Medal Lecture 2022, Wolf Prize in Chemistry 2023 and Japan Academy Prize 2024. He is also a founder of PeptiDream Inc. Tokyo and the Board of Director until 2018. He is also a founder and the Board of Director of MiraBiologics Inc. since 2017.

Presentation

Macrocyclic Peptides, Pseudo-Natural Macrocycles and NeoBiologics for Therapeutics Innovation

Macrocyclic peptides possess a number of pharmacological characteristics distinct from other well-established therapeutic molecular classes, resulting in a versatile drug modality with a unique profile of advantages. Macrocyclic peptides are accessible by not only chemical synthesis but also ribosomal synthesis. Particularly, recent inventions of the genetic code reprogramming integrated with an in vitro display format, referred to as RaPID (Random non-standard Peptides Integrated Discovery) system, have enabled us to screen mass libraries over trillion members of macrocyclic peptides and discover de novo bioactive molecules. This technology was further integrated with post-translational modifying enzymes to discover pseudo-natural products. Moreover, we have recently developed a LassoGraft technology where a pharmacophore sequence of macrocycle is grafted (i.e. replaced) into a loop of a protein of interest, yielding a protein that has a binding ability of the parental macrocycle has. We referred such proteins to as NeoBiologics. This lecture discusses these technologies, leading to potentials for the therapeutics innovation.

Plenary Lecture IV

Prof. James C. Liao

President of Academia Sinica

Taiwan

H-index: 111 (record from Google Scholar)

Research

• Synthetic Biology
• Metabolic Engineering
• Systems Biology

Background

Dr. James C. Liao, President of Academia Sinica, Taiwan, is an elected Member of the US National Academy of Engineering, US National Academy of Sciences, and Academician of Academia Sinica in Taiwan. After working as a research scientist at Eastman Kodak Company, he started his academic career at Texas A&M University in 1990 and moved to UCLA in 1997 until he assumed the current position in 2016.

He is a pioneer in Metabolic Engineering and Synthetic Biology. His research has focused on metabolism, including its biochemistry, regulation, design, and evolution. Dr. Liao received numerous awards and recognitions, including the US EPA Presidential Green Chemistry Challenge Award, the White House “Champion of Change” for innovations in renewable energy, the ENI Renewable Energy Prize, Italy, the US National Academy of Sciences Award for the Industrial Application of Science, Novozyme Award for Excellence in Biochemical and Chemical Engineering, and the Israeli Samson-Prime Minister's Prize for Innovation in Alternative Energy and Smart Mobility for Transportation.

Presentation

Evolutionary engineering of methylotrophic E. coli

As methanol can be derived from either CO2 or methane, methanol economy can play an important role in combating climate change. In this scenario, rapid utilization of methanol by an industrial microorganism is the first and crucial step for efficient utilization of the C1 feedstock chemical. We have developed a methylotrophic E. coli strain with a doubling to me of 3.5 hours under optimal conditions, comparable or faster than native model methylotrophs Methylorubrum extorquens AM1 (Td~4hr) and Bacillus methanolicus at 37°C (Td~5hr). To accomplish this, we developed a bacterial artificial chromosome (BAC) with dynamic copy number variation (CNV) to facilitate overcoming the formaldehyde-induced DNA-protein cross-linking (DPC) problem in the evolution process. We tracked the genome variations of 75 cultures along the evolution process by next-generation sequencing, and identified the features of the fast-growing strain. After stabilization, the final strain grew to 20 g/L of cell mass within 77 hrs in a bioreactor. This study illustrates the potential of dynamic CNV as an evolution tool and synthetic methylotrophs as a platform for sustainable biotechnological applications.

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