Emily Balskus

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.

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. 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.

Balskus received a B.A. with highest honor in chemistry, summa cum laude, in 2002 from Williams College, where she published her first paper on the synthesis of (-)-hennoxazole A in the lab of professor Thomas E. Smith. 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. 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.

Research The Balskus lab's research is centered on 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. 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.

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." 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.

Another key publication, A prominent glycyl radical enzyme in human gut microbiomes metabolizes trans-4-hydroxy-L-proline 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." 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. 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. The success of these aforementioned approaches suggests that microbial growth and activity can be controlled and utilized for various chemical production applications. 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

Volunteering Balskus was a co-organizer of the 2019 Keystone Symposia 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 to improve the field of microbiome research.

Awards and honors

2020 - Alan T. Waterman Award 2019 - Tetrahedron Young Investigator Award 2019 - Laureate in Chemistry, Blavatnik Award for Young Scientists 2019 - Saltman Award Lecture, Metals in Biology Gordon Research Conference 2018 - Science News "10 Scientists to Watch" 2017 - Pfizer Award in Enzyme Chemistry 2016 - Hirata Award, Nagoya University and the Hirata Foundation 2016 - HHMI-Gates Faculty Scholar 2015 - Chemical and Engineering News Talented Twelve 2015 - Camille Dreyfus Teacher-Scholar Award 2015 - Cottrell Scholar Award 2015 - NSF CAREER Award 2015 - ACS "Talented 12" Award 2014 - MIT Technology Review Innovator Under 35 2014 - Royal Society of Chemistry Natural Products Reports Emerging Investigator Lectureship 2014 - Sloan Research Fellowship 2014 - Thieme Chemistry Journal Awardee 2014 - Damon Runyon–Rachleff Innovation Award 2013 - George W. Merck Fellowship 2013 - Kavli Fellow, National Academy of Sciences 2012 - NIH Director's New Innovator Award 2012 - Searle Scholars Program