Plenary Lecture I

Prof. Jens Nielsen

Professor of Biology and Biological Engineering at Chalmers University of Technology
CEO of BioInnovation Institute

Sweden

TIME: October 5 (Thursday), 2023, 09:00-09:40

PLACE: Grand Ballroom (3F)

Publications: 800 (record from lab website)

h-index: 153 (record from Google Scholar)

Research

• Metabolic engineering
• Metabolism
• Systems biology
• Synthetic biology
• Industrial biotechnology

Background

He is an internationally respected scientist who has published more than 850 scientific articles that have been cited more than 110,000 times and with a current H-index of 152. He has received numerous awards, including the Novozymes Prize, the ENI Prize, the Eric and Sheila Samson Prime Ministers Prize for Innovation in Alternative Fuels for Transportation, Nature Award for Mentoring, the Emil Chr. Hansen Gold Medal, and the Gold Medal from the Royal Swedish Academy of Engineering Sciences. In 2019 he was honored as Knight, Ridder af Dannebrog, by Her Majesty The Queen of Denmark, for his meritorious service and contribution to science.

Jens Nielsen has been elected into several academies, including the Royal Swedish Academy of Sciences, the Royal Danish Academy of Science and Letters, the National Academy of Sciences (USA), the National Academy of Engineering (USA), and the Chinese Academy of Engineering. Jens Nielsen has several years of entrepreneurial expertise as the founder of biotech companies such as Fluxome A/S, MycoTeQ A/S, MetaboGen AB, Melt&Marble AB, Elypta AB, and Chrysea Inc.

Presentation

Metabolic Engineering of Yeast

Synthetic Biology relies on the Design-Build-Test cycle. This cycle includes technologies like mathematical modeling of metabolism, genome editing and advanced tools for phenotypic characterization. In recent years there have been advances in several of these technologies, which has enabled faster development of metabolically engineered strains that can be used for production of fuels and chemicals.

The yeast Saccharomyces cerevisiae is widely used for production of foods and beverages, but also food ingredients and dietary supplements. Through metabolic engineering of this yeast a number of novel industrial processes have been developed over the last 10 years. Besides its wide industrial use, S. cerevisiae also serves as an eukaryal model organism, and many systems biology tools have therefore been developed for this organism. These tools can be used for detailed phenotypic characterization as well as for metabolic design.

In this lecture it will be demonstrated how the Design-Build-Test cycle has allowed for development of yeast cell factories for production of a range of different chemicals, many that find application as food ingredients. Some examples of different technologies will be presented together with examples of metabolic designs, in particular for development of platform strains that can be used for production of a fatty acid derived products, e.g. fatty alcohols. It will be argued that with advancement in genome-editing technologies and novel methods for rapid phenotypic screening, advancement in the field is hampered by our design abilities, i.e. to predict genotype-phenotype connections. For this genome-scale metabolic models is a strong technology, and in the presentation recent advancements in the integration of mathematical modeling with multi-omics analysis for cell factory design will be presented.

Plenary Lecture II

Prof. Dina Petranovic Nielsen

Professor of Technical University of Denmark, Denmark
Chief Scientific(CSO) and Chief Partnership(CPO)
Officer at The Novo Nordisk Foundation Center for Biosustainability

Denmark

TIME: October 5 (Thursday), 2023, 09:40-10:20

PLACE: Grand Ballroom (3F)

Background

Dina has the background in molecular and cell biology. She worked for 10 years as Assistant and Associate professor at Chalmers University of Technology. After graduating with an MBA. she moved to the Novo Nordisk Foundation as Senior Scientific manager for Biotechnology, where she was responsible for development of the Biotech strategy. After that she joined the Technical University of Denmark, where she is the Chief Scientific and Chief Partnerships Officer at the Novo Nordisk Foundation Center for Biosustanability, and also member of the university strategy team for development of biotech strategy.

Presentation

Biotechnology for Impact

In this presentation I will give an overview of the Novo Nordisk Foundation Center for Biosustanability history, development and strategy from its inceptions to future plans, as well as strategic developments in biotechnology within the Technical University of Denmark and the funding agency, the Novo Nordisk Foundation.

I will also provide some reflections and lessons we have learned in research and innovation, as the center grew from a handful of people to more than 300 and as we pivoted several times over the course of a decade.

Plenary Lecture III

Prof. Jay D. Keasling

Professor of Chemical & Biomolecular Engineering at University of California, Berkeley

USA

TIME: October 5 (Thursday), 2023, 14:30-15:10

PLACE: Grand Ballroom (3F)

Publications: 430 (record from lab website)

h-index: 133 (record from Google Scholar)

Research

• Metabolic engineering
• Synthetic biology

Background

Jay Keasling is a pioneer in engineering microbes and metabolism. During the early 2000s, Jay led a UC Berkeley research team to use engineered yeast to synthetically produce artemisinin, the powerful anti-malarial drug. Researchers at the Keasling Lab are now using the same technology to produce other pharmaceuticals, commodity chemicals, and cellulosic biofuels.

Presentation

Production of Supply-Limited Natural Product Therapeutics Using Engineered Yeast

Plants produce some of the most potent human therapeutics and have been used for millennia to treat illnesses. Two examples are vinblastine, the chemotherapeutic, and QS-21, an adjuvant used in several vaccines. Both molecules are large, highly decorated terpenes. Vinblastine is extracted from Catharanthus roseus and requires 1ton of dried leaves to obtain 1 g. In a similar vein, QS-21 is extracted from the tree bark of Quillaja saponaria, and its isolation is complicated as the plant extract contains a multitude of different structurally related Quillaja saponins, rendering the purification process highly laborious and low yielding. To alleviate supply issues, we have engineered Saccharomyces cerevisiae to produce these molecules.

For production of vinblastine, we have demonstrated de novo microbial biosynthesis of vindoline and catharanthine using a highly engineered yeast, and in vitro chemical coupling to vinblastine. We introduced 30 enzymatic steps beyond the yeast native metabolites geranyl pyrophosphate and tryptophan to catharanthine and vindoline. In total, 56 genetic edits were performed, including expression of 34 heterologous genes from plants as well as deletions, knock-downs, and overexpression of ten yeast genes to improve precursor supplies towards de novo production of catharanthine and vindoline, from which semi-synthesis to vinblastine occurs. As the vinblastine pathway is one of the longest monoterpene indole alkaloid biosynthetic pathways, this study positions yeast as a scalable platform to produce more than 3,000 natural MIAs and virtually infinite new-to-nature analogues.

For QS-21 biosynthesis, we upregulated the yeast native mevalonate pathway to provide a high carbon flux towards 2,3-oxidosqualene, which is then cyclized by a heterologous β-amyrin synthase and site-selectively oxidized by plant cytochrome P450s to yield quillaic acid, the aglycone of QS-21. We further introduced plant nucleotide sugar synthetic pathways to make seven non-native UDP-sugars, which are used to add sugars onto the C3 hydroxy and C28 carboxy functional groups of quillaic acid via the co-expression of QS-21 pathway glycosyltransferases. Furthermore, an engineered type I PKS LovF, two type III polyketide synthases (PKSs), as well as two standalone ketoreductases (KRs) were expressed in yeast to form the dimeric acyl unit that constitutes the last step prior to the terminal arabinofuranose addition to yield QS- 21. Owing to the promiscuity of several enzymes, structural analogues of QS-21 have further been generated and characterized using the biosynthetic platform, allowing for future establishment of a structure-bioactivity relationship as well as the rational design of novel potent vaccine adjuvants.

Plenary Lecture IV

Prof. Rolf Müller

Professor of Microbial Natural Products at Saarland University
Director of Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and Helmholtz Centre for Infection

Germany

TIME: October 5 (Thursday), 2023, 15:10-15:50

PLACE: Grand Ballroom (3F)

Publications: ~500 (record from lab website)

h-index: 92 (record from Google Scholar)

Research

• Natural products
• Biosynthesis
• Myxobacteria
• Genome mining

Background

Rolf Müller is Managing Director of the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) since 2009, and heads the Department of “Microbial Natural Products” (MINS). Since October 2003, he has held a chair as professor of Pharmaceutical Biotechnology at Saarland University.

Rolf is involved in several national and international research networks and collaborations with the aim to identify novel bioactive natural products, to analyze their biosynthesis and structures and to develop their biological and chemical properties towards novel (pre)clinical candidates. He is elected member of both acatech and Leopoldina as well as honorary professor of the Shandong University joint Helmholtz Institute of Biotechnology, which has recently been recognized as Helmholtz International Laboratory for Antiinfectives. In 2021, he was awarded the Gottfried Wilhelm Leibniz-Prize.

Rolf studied pharmacy in Bonn, where he also obtained his PhD in 1994. After a two-year research scholarship at the University of Washington in Seattle, he became junior group leader at the Gesellschaft für Biotechnologische Forschung in Braunschweig. In 2000, he completed his habilitation thesis at the Technische Universität Braunschweig on the biosynthesis of antibiotics in actinomycetes and myxobacteria.

Presentation

Microorganisms as a Source of Innovative Compounds against Drug Resistant Bacterial Pathogens

Amongst the well-established bacterial producers, myxobacteria have a great track record for the discovery of entirely new natural product (NP) scaffolds exhibiting promising bioactivities. Comparisons of myxobacterial metabolite profiles with the number of underlying biosynthetic gene clusters encoded in their large genomes show, that many compounds still remain unknown. Further, recent studies indicate that the order of myxobacteria likely comprises many more biodiverse representatives than previously assumed. According to metagenomics analyses, myxobacteria (including many underexplored representatives) are highly abundant in the soil microbiome, where they play a crucial role in soil nutrient and carbon cycling. Taken together with our recent genomic analyses, these findings suggest that the biosynthetic potential of myxobacteria is a long way from being exhausted.

We recently demonstrated that chemical diversity correlates with taxonomic distance in myxobacteria. Accordingly, we are more likely to isolate novel compound classes from strains which are phylogenetically distant from previously characterized strains as compared to closely related strains. This knowledge can be applied to prioritize strains for natural product discovery, thus increasing the chance of discovering compound classes with yet unknown chemical structures and biological activities. I will discuss recent results from our laboratory regarding the identification of novel bioactive NPs from myxobacteria based on different approaches, and show our recent advances in their preclinical development.

Keywords

Natural products, antimicrobial activity, antimicrobial resistance

Plenary Lecture V

Editor-in-Chief Magdalena Skipper

Editor-in-Chief of Nature

UK

TIME: October 6 (Friday), 2023, 09:00-09:40

PLACE: Grand Ballroom (3F)

Background

Dr Magdalena Skipper is Editor in Chief of Nature and Chief Editorial Advisor for the Nature portfolio. A geneticist by training, she holds a PhD from University of Cambridge, UK. She has considerable editorial and publishing experience, having worked as Chief Editor of Nature Reviews Genetics, Senior Editor for genetics and genomics at Nature and Editor in Chief of Nature Communications. She is passionate about mentorship, research integrity, as well as collaboration and inclusion in research. As part of her desire to promote underrepresented groups in research, in 2018 she co-launched the Nature Research Inspiring Science Award for women early-career researchers.

Presentation

Nature & Journal Publishing in the 21st Century – Holding up a Mirror to Science

Today’s research needs to be transparent, inclusive, collaborative and open. Achieving this ambitious vision requires that all stakeholders in the research ecosystem play their part. So how can editors and publishers support this goal? And how can researchers work most effectively with the editors and publishers?

Plenary Lecture VI

Prof. V. Narry Kim

Professor of Biological Sciences at Seoul National University
Director of Center for RNA Research, Institute for Basic Science

Korea

TIME: October 6 (Friday), 2023, 09:40-10:20

PLACE: Grand Ballroom (3F)

Publications: 116 (record from lab website)

h-index: 68 (record from Google Scholar)

Research

• microRNA
• RNA modifications
• RNA binding proteins

Background

Narry Kim is a Professor in the School of Biological Sciences at Seoul National University and a founding director of Center for RNA Research at Institute for Basic Science. She received her Ph.D. in 1998 from the University of Oxford where she studied lentiviruses and gene delivery. With keen interest in RNA biology, she joined the Gideon Dreyfuss lab at the University of Pennsylvania and researched the role of the exon junction complex in mRNA surveillance. Her current research group investigates how genes are regulated at the RNA level, with particular interests in microRNA, mRNA, and viral RNA. She is a recipient of the L’Oreal-UNESCO Women in Science Award, Hoam Prize, and Asan Prize, and a member of KAS, NAS and EMBO.

Presentation

mRNA Mixed Tailing and Its Implication in mRNA Therapeutics

Poly(A) tail of mRNA plays a key role in mRNA stability control as deadenylation is the rate-limiting step in mRNA degradation. Moreover, poly(A) tail promotes translation by binding to PABPC which in turn interacts with translation initiation factors. We found that poly(A) tails of some mRNAs contain non-adenosine residues, which we named as “mixed tails”. TENT4 enzymes (TENT4A and TENT4B) generate “mixed tails” on mRNAs by adding adenosines with intermittent non-adenosine residues, which protect mRNAs from deadenylation. We further discovered that the transcripts of two distinct DNA viruses, hepatitis B virus (HBV) and human cytomegalovirus (HCMV), are heavily modified and regulated critically by mixed tailing.

Because the number of sequenced viral genomes has increased greatly, presenting an opportunity to understand viral diversity and uncover unknown regulatory mechanisms, we recently conducted functional screens of 30,367 viral segments from 143 species representing 96 genera and 37 families. Using a library of viral segments in 3UTR, we identified hundreds of elements impacting RNA abundance and translation. To illustrate the power of this approach, we investigated K5, an element conserved in kobuviruses, and found its potent ability to enhance mRNA stability and translation. Moreover, we identified a previously uncharacterized protein, ZCCHC2, as a critical host factor for K5. ZCCHC2 recruits the terminal nucleotidyl transferase TENT4 to elongate poly(A) tails with mixed sequences, delaying deadenylation. K5 increases protein expression and stability in various contexts including plasmids, adeno-associated viral vectors, and in vitro transcribed mRNAs. This study provides a unique resource for virus and RNA research and offers valuable regulatory elements for gene therapy and mRNA therapeutics.

Keywords

mRNA, RNA stability, translation, poly(A) tail, mixed tail, mRNA therapeutics

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