Emily Balskus

Last updated
Emily Balskus
Born1980 (age 42–43)
CitizenshipUnited States
Alma mater Williams College, Harvard University
Scientific career
FieldsChemical Biology, Enzymology, Microbiology, Biochemistry
Institutions Harvard University
Website https://www.microbialchemist.com/

Emily P. Balskus is an American chemical biologist, enzymologist, microbiologist, and biochemist born in Cincinnati, Ohio in 1980. She has been on the faculty of the Chemistry and Chemical Biology department of Harvard University since 2011 and is currently the Morris Kahn Professor. She has published more than 80 peer-reviewed papers and three book chapters. Since 2012 she has been invited to give over 170 lectures, has held positions on various editorial boards, and served as a reviewer for ACS and Nature journals among others. Balskus also currently serves as a consultant for Novartis, Kintai Therapeutics, and Merck & Co.

Contents

Early life and education

Balskus was already interested in a potential career in science in elementary school where she conducted a science fair experiment on dilution and conservation of matter. [1] Later in high school she was introduced to chemistry and was "captivated by the excitement of manipulating molecules in lab." Later in her scientific career this evolved into her fascination of how molecules are made in living organisms. In an interview for the Blavatnik Awards for Young Scientists, Balskus reflects that she was likely inspired to go into science because all of her science teachers were women. [2]

Balskus received a B.A. with highest honor in chemistry, summa cum laude, in 2002 from Williams College, [3] [4] where she published her first paper on the synthesis of (-)-hennoxazole A in the lab of professor Thomas E. Smith. [5] She then went on to the University of Cambridge as a Churchill Scholar where she earned a M.Phil. in chemistry in the lab of Steven V. Ley. [3] [4] Balskus received her Ph.D. with organic chemist, Eric Jacobsen, at Harvard in 2008. There she proposed the novel idea of using an asymmetric catalyst to control chemical bond formation across large, cyclic molecules to form the favored stereoisomer. [6] She then made the switch from organic chemistry to chemical biology as she pursued a postdoctoral fellowship from 2008 through 2011 at Harvard Medical School with natural products researcher Christopher Walsh. Together they collaborated on the biosynthesis of scytonemin, a "microbial sunscreen" used to protect microorganisms from harmful UV light. [4] In 2009 she became a member of the Microbial Diversity Summer Course at the Marine Biology Lab at Woods Hole and received training in microbial ecology and environmental microbiology. [7]

Research

The Balskus lab's research is centered around the human microbiome, which is the trillions of commensal, symbiotic, and pathogenic microorganisms that live in and on us. These microorganisms include bacteria, protozoa, and viruses. Because of the abundance of genes in the human microbiome (200 times the amount in the human genome) many enzymes and/or their mechanisms have not been characterized. [8] Two of Balskus' aims is therefore to elucidate the mechanisms by which these microbial enzymes perform chemistry and to identify the specific microbes, genes, and enzymes responsible for key metabolic activities. A third aim is to develop biocompatible methods to control, manipulate, and study microbial chemistry in situ. [9]

Bioinformatics is heavily applied in the Balskus lab in order to study the extensive amount of genes of the human microbiome. Bioinformatics is the "science of storing, retrieving and analysing large amounts of biological information." [10] Examples of bioinformatic analyses utilized in the Balskus lab are; phylogenetics, sequence alignments, homology modeling, and DNA annotation. A key accomplishment of the Balskus lab was the elucidation of the enzyme responsible for the already known conversion of choline to trimethylamine, choline trimethylamine-lyase. They identified the gene cluster required for the cleavage of the C-N bond of choline and hypothesized that it coded for a glycyl radical enzyme (GRE), a class of enzymes not previously reported to perform that type of chemistry. Sequence alignments of the gene cluster and previously functionally characterized glycyl radical enzymes as well as homology models of the suspected enzyme revealed the presence of conserved key glycine and cysteine residues in the active site, supporting the hypothesis that the enzyme is a member of the GRE family of enzymes. This research is important because choline metabolism has possible links to fish malodor syndrome, non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular disease. [11]

Another key publication, A prominent glycyl radical enzyme in human gut microbiomes metabolizes trans-4-hydroxy-L-proline [12] outlines an important research approach utilized by Balskus and her team; chemically-guided functional profiling. First an enzyme family of interest is identified (in this case, the GRE family) and the amino acid sequences of all the members are compared. With the knowledge of the structures and functions of already characterized members of the enzyme family and the amino acid residues responsible, a sequence similarity network (SSN) is constructed to group together sequences of enzymes in clusters that share biological function. The SSN is used to interpret data generated by Short-BRED, a quantitative metagenomic analysis tool which uses the amino acid sequences of the enzyme family as input. Short-BRED identifies the unique sequence markers of each group of similar members and sequentially determines their abundance in the human microbiome. This tool can be used to identify uncharacterized members and prioritize their study based on their abundance.

Biocompatible chemistry is another integral strategy in the Balskus lab. These transformations are defined as "non-enzymatic chemical reactions that interact with the metabolism of living organisms in a way that alters biological function." [13] They have been able to develop biocompatible cyclopropanation and hydrogenation reactions to alter the reactivity of microbes by using non-enzymatic catalysts, iron(III) phthalocyanine and palladium, respectively. [14] [15] Another application of this approach used by Balskus is to rescue the activity of auxotrophic microbes with the use of transition metal-catalyzed reactions. This approach produces the essential nutrients that are needed for the growth and survival of the microbes by a non-native route. [13] They were able to rescue an auxotroph lacking the ability to produce p-aminobenzoic acid (PABA), a precursor to folic acid by using a ruthenium catalyst. [16] The success of these aforementioned approaches suggests that microbial growth and activity can be controlled and utilized for various chemical production applications. [13]

A recent achievement (2019) of the Balskus lab was elucidating the mechanism by which the genotoxin, colibactin, damages DNA. They found that a cyclopropane "warhead" breaks the DNA strands through an alkylation reaction. [17] Other areas of research investigated by the Balkus lab is microbe drug metabolism. In an interview with The Scientist magazine, Balskus pointed out that many drugs such as digoxin [6] and byproducts of human metabolism can be degraded by gut bacteria, leading to lowered effects of these molecules than would be expected. Overall, the work done by the Balskus lab presents the foundational strategies needed to investigate the human microbiome and to understand how it affects our health. Their hope is to influence the development of therapeutic strategies that work not on the human host, but on their microbiome instead. [18]

Volunteering

Balskus was a co-organizer of the 2019 Keystone Conference [19] on chemical and biological considerations of the gut microbiota. The major charge of this conference was to "...adopt other disciplines" such as xenobiology, ecology, and interspecies communication [20] to improve the field of microbiome research.

Awards and honors

Related Research Articles

<span class="mw-page-title-main">Metabolism</span> Set of chemical reactions in organisms

Metabolism is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the conversion of food to building blocks for proteins, lipids, nucleic acids, and some carbohydrates; and the elimination of metabolic wastes. These enzyme-catalyzed reactions allow organisms to grow and reproduce, maintain their structures, and respond to their environments. The word metabolism can also refer to the sum of all chemical reactions that occur in living organisms, including digestion and the transportation of substances into and between different cells, in which case the above described set of reactions within the cells is called intermediary metabolism.

<span class="mw-page-title-main">Choline</span> Chemical compound and essential nutrient

Choline is a cation with the chemical formula [(CH3)3NCH2CH2OH]+. Choline forms various salts, for example choline chloride and choline bitartrate.

<span class="mw-page-title-main">Human microbiome</span> Microorganisms in or on human skin and biofluids

The human microbiome is the aggregate of all microbiota that reside on or within human tissues and biofluids along with the corresponding anatomical sites in which they reside, including the skin, mammary glands, seminal fluid, uterus, ovarian follicles, lung, saliva, oral mucosa, conjunctiva, biliary tract, and gastrointestinal tract. Types of human microbiota include bacteria, archaea, fungi, protists, and viruses. Though micro-animals can also live on the human body, they are typically excluded from this definition. In the context of genomics, the term human microbiome is sometimes used to refer to the collective genomes of resident microorganisms; however, the term human metagenome has the same meaning.

<span class="mw-page-title-main">Transferase</span> Class of enzymes

A transferase is any one of a class of enzymes that catalyse the transfer of specific functional groups from one molecule to another. They are involved in hundreds of different biochemical pathways throughout biology, and are integral to some of life's most important processes.

Trimethylamine (TMA) is an organic compound with the formula N(CH3)3. It is a colorless, hygroscopic, and flammable tertiary amine. It is a gas at room temperature but is usually sold as a 40% solution in water. (It is also sold in pressurized gas cylinders.) TMA is a nitrogenous base and can be readily protonated to give the trimethylammonium cation. Trimethylammonium chloride is a hygroscopic colorless solid prepared from hydrochloric acid. Trimethylamine is a good nucleophile, and this reaction is the basis of most of its applications. TMA is widely used in industry: it is used in the synthesis of choline, tetramethylammonium hydroxide, plant growth regulators or herbicides, strongly basic anion exchange resins, dye leveling agents, and a number of basic dyes. At higher concentrations it has an ammonia-like odor, and can cause necrosis of mucous membranes on contact. At lower concentrations, it has a "fishy" odor, the odor associated with rotting fish.

<span class="mw-page-title-main">Gut microbiota</span> Community of microorganisms in the gut

Gut microbiota, gut microbiome, or gut flora, are the microorganisms, including bacteria, archaea, fungi, and viruses, that live in the digestive tracts of animals. The gastrointestinal metagenome is the aggregate of all the genomes of the gut microbiota. The gut is the main location of the human microbiome. The gut microbiota has broad impacts, including effects on colonization, resistance to pathogens, maintaining the intestinal epithelium, metabolizing dietary and pharmaceutical compounds, controlling immune function, and even behavior through the gut–brain axis.

Joanna Sigfred Fowler is a scientist emeritus at the U.S. Department of Energy's Brookhaven National Laboratory in New York. She served as professor of psychiatry at Mount Sinai School of Medicine and director of Brookhaven's Radiotracer Chemistry, Instrumentation and Biological Imaging Program. Fowler studied the effect of disease, drugs, and aging on the human brain and radiotracers in brain chemistry. She has received many awards for her pioneering work, including the National Medal of Science.

Jeffrey I. Gordon is a biologist and the Dr. Robert J. Glaser Distinguished University Professor and Director of the Center for Genome Sciences and Systems Biology at Washington University in St. Louis. He is internationally known for his research on gastrointestinal development and how gut microbial communities affect normal intestinal function, shape various aspects of human physiology including our nutritional status, and affect predisposition to diseases. He is a member of the National Academy of Sciences, the American Academy of Arts and Sciences, the Institute of Medicine of the National Academies, and the American Philosophical Society.

<span class="mw-page-title-main">Human Microbiome Project</span> Former research initiative

The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on identifying and characterizing human microbiota. The second phase, known as the Integrative Human Microbiome Project (iHMP) launched in 2014 with the aim of generating resources to characterize the microbiome and elucidating the roles of microbes in health and disease states. The program received $170 million in funding by the NIH Common Fund from 2007 to 2016.

<span class="mw-page-title-main">Microbiome</span> Microbial community assemblage and activity

A microbiome is the community of microorganisms that can usually be found living together in any given habitat. It was defined more precisely in 1988 by Whipps et al. as "a characteristic microbial community occupying a reasonably well-defined habitat which has distinct physio-chemical properties. The term thus not only refers to the microorganisms involved but also encompasses their theatre of activity". In 2020, an international panel of experts published the outcome of their discussions on the definition of the microbiome. They proposed a definition of the microbiome based on a revival of the "compact, clear, and comprehensive description of the term" as originally provided by Whipps et al., but supplemented with two explanatory paragraphs. The first explanatory paragraph pronounces the dynamic character of the microbiome, and the second explanatory paragraph clearly separates the term microbiota from the term microbiome.

B. Brett Finlay, is a Canadian microbiologist well known for his contributions to understanding how microbes cause disease in people and developing new tools for fighting infections, as well as the role the microbiota plays in human health and disease. Science.ca describes him as one of the world's foremost experts on the molecular understanding of the ways bacteria infect their hosts. He also led the SARS Accelerated Vaccine Initiative (SAVI) and developed vaccines to SARS and a bovine vaccine to E. coli O157:H7. His current research interests focus on pathogenic E. coli and Salmonella pathogenicity, and the role of the microbiota in infections, asthma, and malnutrition. He is currently the UBC Peter Wall Distinguished Professor and a Professor in the Michael Smith Laboratories, Microbiology and Immunology, and Biochemistry and Molecular Biology, and Co-director and Senior Fellow for the CIFAR Humans and Microbes program. He is also co-author of the book Let Them Eat Dirt: Saving Your Child from an Oversanitized World and The Whole-Body Microbiome: How to Harness Microbes - Inside and Out - For Lifelong Health. Finlay is the author of over 500 publications in peer-reviewed journals and served as editor of several professional publications for many years.

<span class="mw-page-title-main">Pharmacomicrobiomics</span>

Pharmacomicrobiomics, proposed by Prof. Marco Candela for the ERC-2009-StG project call, and publicly coined for the first time in 2010 by Rizkallah et al., is defined as the effect of microbiome variations on drug disposition, action, and toxicity. Pharmacomicrobiomics is concerned with the interaction between xenobiotics, or foreign compounds, and the gut microbiome. It is estimated that over 100 trillion prokaryotes representing more than 1000 species reside in the gut. Within the gut, microbes help modulate developmental, immunological and nutrition host functions. The aggregate genome of microbes extends the metabolic capabilities of humans, allowing them to capture nutrients from diverse sources. Namely, through the secretion of enzymes that assist in the metabolism of chemicals foreign to the body, modification of liver and intestinal enzymes, and modulation of the expression of human metabolic genes, microbes can significantly impact the ingestion of xenobiotics.

Alison Butler is a Distinguished Professor in the Department of Chemistry and Biochemistry at the University of California, Santa Barbara. She works on bioinorganic chemistry and metallobiochemistry. She is a Fellow of the American Association for the Advancement of Science (1997), the American Chemical Society (2012), the American Academy of Arts and Sciences (2019), and the Royal Society of Chemistry (2019). She was elected a member of the National Academy of Sciences in 2022.

Elizabeth S. Sattely is an American scientist and biotechnology engineer. She is an Associate Professor of Chemical Engineering in the Department of Chemical Engineering, an HHMI investigator, and a ChEM-H Faculty Fellow at Stanford University.

<span class="mw-page-title-main">Janelle Ayres</span> American immunologist

Janelle S. Ayres is an American immunologist and microbiologist, member of the NOMIS Center for Immunobiology and Microbial Pathogenesis and Helen McLoraine Developmental Chair at the Salk Institute for Biological Sciences. Her research focuses on the relation of host-pathogen interactions with the microbiome.

Emily A. Weiss is the Mark and Nancy Ratner Professor of Chemistry and Director of the Photo-Sciences Research Center at Northwestern University. Her research considers the optical and electronic properties of nanostructures, including hybrid organic–inorganic quantum dots. She was a two-time finalist in the Blavatnik Awards for Young Scientists.

<span class="mw-page-title-main">Peter J. Turnbaugh</span> American microbiologist (born c. 1981)

Peter J. Turnbaugh is a microbiologist and a professor at University of California, San Francisco. He is known for his research on the metabolic activities performed by the trillions of microbes that colonize humans' adult bodies. Turnbaugh and his research group use interdisciplinary approaches in preclinical models and human cohorts to study the mechanisms through which the gut microbiome influences nutrition and pharmacology.

Catalina Cuellar Gempeler is a Colombian microbial ecologist and marine microbiologist, currently teaching and doing research at Cal Poly Humboldt. Her research focuses mainly on understanding microbial meta-community, eco-evolutionary dynamics, and ecosystem dynamics. The Catalina Cuellar-Gempeler lab is currently focused on studying the interactions between hosts and their microbial communities. The lab's main emphasis is on the microbes used in digestion in the Californian and Eastern, carnivorous pitcher plants. In March 2021, Cuellar-Gempeler was awarded an Early Career grant for $1 million by the National Science Foundation.

Lesley Hoyles is a Welsh microbiologist who is Professor of Microbiome and Systems Biology at Nottingham Trent University. She combines in vivo and in vitro microbiology and bioinformatics research to better understand how the gut microbiota influences health and disease.

<span class="mw-page-title-main">Elaine Hsiao</span> American biologist and academic

Elaine Yih-Nien Hsiao is an American biologist who is Professor in Biological Sciences at University of California, Los Angeles. Her research considers the microbes that impact human health. She was a 2022 Laureate for the Blavatnik Awards for Young Scientists.

References

  1. 1 2 Ehrenberg, Rachel (2018-09-28). "Emily Balskus uses chemical logic to study the microbiome". Science News. Retrieved 2018-10-29.
  2. ↑ Emily Balskus, 2019 Blavatnik National Laureate in Chemistry.
  3. 1 2 3 "Arthur C. Cope Scholar Awards: Emily P. Balskus | January 15, 2018 Issue - Vol. 96 Issue 3 | Chemical & Engineering News". cen.acs.org. Retrieved 2018-10-19.
  4. 1 2 3 "Balskus Lab - People - Emily". Balskus Lab Website. Retrieved 26 October 2018.
  5. ↑ Smith, Thomas E.; Kuo, Wen-Hsin; Bock, Victoria D.; Roizen, Jennifer L.; Balskus, Emily P.; Theberge, Ashleigh B. (2007-03-15). "Total synthesis of (-)-hennoxazole A". Organic Letters. 9 (6): 1153–1155. doi:10.1021/ol070244p. ISSN   1523-7060. PMID   17316014.
  6. 1 2 "Emily Balskus Pins Down the Chemistry and Metabolism of Human Microbiomes". The Scientist Magazine®. Retrieved 2018-10-19.
  7. ↑ Emily https://www.microbialchemist.com/people/emily
  8. ↑ Marilyn Hair & Jon Sharpe. The Center for Ecogenetics and Environmental Health, University of Washington, 1/2014.
  9. ↑ Emily Balskus, 2019 Blavatnik National Laureate in Chemistry. https://www.youtube.com/watch?v=c_qFNuVJw8Q&feature=emb_logo
  10. ↑ What is bioinformatics? https://www.ebi.ac.uk/training/online/course/bioinformatics-terrified/what-bioinformatics-0
  11. ↑ Craciun, Smaranda; Balskus, Emily P. “Microbial Conversion of Choline to Trimethylamine Requires a Glycyl Radical Enzyme.” Proceedings of the National Academy of Sciences USA 2012, 109, 21307–21312. doi:10.1073/pnas.1215689109
  12. ↑ Levin, Benjamin J.*; Huang, Yolanda Y.*; Peck, Spencer C.; Wei, Yifeng; Martinez-del Campo, Ana; Marks, Jonathan A.; Franzosa, Eric A.; Huttenhower, Curtis; Balskus, Emily P. “A Prominent Glycyl Radical Enzyme in Human Gut Microbiomes Metabolizes trans-4-Hydroxy-L-Proline.” Science 2017, 355, aai8386. doi:10.1126/science.aai8386
  13. 1 2 3 Manipulating Microbes With Biocompatible Chemistry https://www.microbialchemist.com/biocompatible-chemistry
  14. ↑ Wallace, Stephen; Balskus, Emily P. “Interfacing Microbial Styrene Production with a Biocompatible Cyclopropanation Reaction.” Angew. Chem. Int. Ed. 2015, 54, 7106–7109. doi:10.1002/anie.201502185
  15. ↑ Sirasani, Gopal; Tong, Liuchuan; Balskus, Emily P. "A Biocompatible Alkene Hydrogenation Merges Organic Synthesis with Microbial Metabolism." Angewandte Chemie International Edition 2014, 53, 7785–7786. Chosen as a Research Highlight in Nature 2014, 510, 447. doi:10.1002/anie.201403148
  16. ↑ Lee, Yunmi; Umeano, Afoma; Balskus, Emily P. "Rescuing Auxotrophic Microorganisms with Nonenzymatic Chemistry." Angewandte Chemie International Edition 2013, 53, 11800–11803. Selected as a Very Important Paper (VIP). doi:10.1002/anie.201307033
  17. ↑ Wilson, Matthew R.*; Jiang, Yindi*; Villalta, Peter W.; Stornetta, Alessia; Boudreau, Paul D.; Carrá, Andrea; Brennan, Caitlin A.; Chun, Eunyoung; Ngo, Lizzie; Samson, Leona D.; Engelward, Bevin P.; Garrett, Wendy S.; Balbo, Silvia; Balskus, Emily P. “The human gut bacterial genotoxin colibactin alkylates DNA” Science 2019, 363, eaar7785. doi:10.1126/science.aar7785
  18. ↑ Understanding the Human Microbiome https://www.microbialchemist.com/microbiome
  19. ↑ Balskus, Emily P.; Turnbaugh, Peter J.; Wolan, Dennis W. (2018-07-24). "Announcement of 2019 Keystone Symposia Conference: "Microbiome: Chemical Mechanisms and Biological Consequences"". mSystems. 3 (4). doi:10.1128/mSystems.00115-18. ISSN   2379-5077. PMC   6060284 . PMID   30057942.
  20. ↑ Kenny, Douglas J.; Balskus, Emily P. (2018). "Engineering chemical interactions in microbial communities". Chemical Society Reviews. 47 (5): 1705–1729. doi:10.1039/C7CS00664K. ISSN   0306-0012. PMID   29210396.
  21. ↑ "National Science Foundation Alan T. Waterman Award".
  22. ↑ "Emily Balskus wins Blavatnik Award for Young Scientists". c&en. Retrieved 21 April 2020.
  23. ↑ "Metals in Biology: Discovery, Dissection, Exploitation and Mimicry of Nature's Inorganic Chemistry to Secure the Future". Gordon Research Conferences. Retrieved 21 April 2020.
  24. ↑ "The 12th Hirata Award". Institute of Transformative Bio-Molecules Nagoya University. Institute of Transformative Bio-Molecules. Retrieved 21 April 2020.
  25. ↑ "The Talented 12: Emily Balskus The Microbiome Code Breaker". c&en. 20 May 2015. Retrieved 21 April 2020.
  26. ↑ "Cottrell Scholar Awards - 2015". Research Corporation for Science Advancement. Archived from the original on 19 October 2018. Retrieved 26 October 2018.
  27. ↑ "Award Abstract #1454007". National Science Foundation. Retrieved 21 April 2020.
  28. ↑ "C&EN's Talented 12". Talented 12. 2015-05-20. Retrieved 2018-10-19.
  29. ↑ Bourzac, Katherine. "MIT Technology Review". Technology Review. Retrieved 21 April 2020.
  30. ↑ "Natural Product Reports Emerging Investigator Lectureship winners". Royal Society of Chemistry. Retrieved 21 April 2020.
  31. ↑ "Alfred P. Sloan Research Fellowships 2014" (PDF). Massachusetts Institute of Technology. Retrieved 21 April 2020.
  32. ↑ "Previous Winners". Thieme Chemistry. Retrieved 21 April 2020.
  33. ↑ "New Discoveries and Honors in Cancer Research". Damon Runyon Cancer Research Foundation. Retrieved 21 April 2020.
  34. ↑ "Founding Sources - Balskus Lab". Microbial Chemist.
  35. ↑ "NIH Director's New Innovator Award Recipients". National Institutes of Health. 18 September 2018. Retrieved 21 April 2020.
  36. ↑ "Scholar Profile Emily P. Balskus". Searle Scholars Program. Archived from the original on 5 September 2015. Retrieved 2 June 2023.
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