Webinar Report: Small molecules, big molecules and beyond

Phil Cole, eLife Senior Editor, and guests discussed new areas of interest in chemical biology.
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In our latest Biochemistry and Chemical Biology webinar, a diverse panel of speakers provided an overview of their work, along with their perspectives on new opportunities for applying chemical tools and concepts to the study of biological systems.

Phil Cole (eLife Senior Editor and Professor of Medicine and Biological Chemistry and Molecular Pharmacology at Harvard Medical School, USA), Emily Balskus (Harvard University, USA), Phil Holliger (MRC Laboratory of Molecular Biology, UK), Yamuna Krishnan (The University of Chicago, USA), and Jim Wells (University of California, San Francisco, USA) also reflected on how publishing this work in eLife can help novel techniques and discoveries reach new audiences.

Keys to deciphering the microbiota’s function

Emily Balskus talked about the research of microbial communities as a promising field of study for chemical biology. She discussed the very recent nature of discoveries enabled by DNA sequencing, related to the make-up and diversity of the human microbiome, and their connection with health and disease. Balskus sees chemical biology as a way to unravel how the microbiota functions. She provided insights into how chemical knowledge and tools can help make critical links between sequencing data and microbial metabolites, genes, enzymes and activities. She says using chemical tools to study the microbiota could provide a greater understanding of the mechanisms by which these organisms affect the body, which could improve our ability to intervene therapeutically.

Synthetic materials with genetic properties

Phil Holliger began by reflecting on the great versatility of nucleic acids, including their potential as a source of new and powerful drugs. He also pointed out the inherent chemical limitations to their pharmaceutical applications, which he said can be overcome with non-natural chemistry. Hollinger believes we’re entering a golden age of nucleic acid drugs reaching the clinic, with discoveries such as his development of Xeno Nucleic Acids (XNAs) potentially opening new therapeutic avenues. He sees great potential in current efforts to expand the genetic alphabet, which greatly augments our ability to encode new types of amino acids.

Nucleic acids are the key component that sets biology apart from chemistry, because biology has a memory.

– Phil Holliger, MRC Laboratory of Molecular Biology, UK

Technology empowers biologists to ask better questions

Yamuna Krishnan mentioned the example of the green fluorescent protein and following developments to show how the visualisation of processes taking place inside the cell can offer completely new biological insights.. She also discussed exciting developments in different types of reporting technologies, and her hopes for new tools that could lead to breakthroughs in the near future. Krishnan then shared her own experience of publishing a Tools and Resources article with eLife, and how that brought a new biological research audience to her work.

Surfaceome in health and disease

Jim Wells introduced his research into the proteome of the cell surface, dubbed the surfaceome, and noted that it’s a structure engaged by protein therapeutics and most small-molecule. He’s hoping that, with the tools he and his colleagues have developed to probe it, they’ll find new tumor-specific antigens that can be targeted with antibodies. Wells is optimistic about the potential of such methods to find surface antigens in many disease settings, such as cancer, diabetes, and even senescence – using proteins as detectors and, in time, therapeutics. He then shared some of his insights into detecting surface proteins, using Next-Gen Sequencing with the aid of DNA-barcoded antibodies, to detect how the surfaceome changes in health and disease.

Q&A session with the speakers

The speakers answered questions on topics including: the latest research on receptors of metabolites released by the human microbiome; how the speakers’ novel methods could be used in different settings; and eLife’s appetite for articles covering more specific topics as mentioned by the participants.

Questions and comments are welcome. Please annotate publicly on the article or contact us at hello [at] elifesciences [dot] org.

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