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Environment

C&EN’s Talented 12

These daring young scientists are using chemistry to make the planet a better place

July 5, 2015 | A version of this story appeared in Volume 93, Issue 27
Illustration of a superhero with the Talented 12 logo.

Credit: Will Ludwig/C&EN

 

 
 

Talented 12

  • Class of 2015

We like to pretend that the extraordinary young scientists profiled in the following pages gather regularly in a secret lair to plot how they’ll fight global scourges such as climate change and human disease.

Editors can dream, right? Although the CO2 Wrangler and the Mind Mapper, as we’ve dubbed them, don’t actually belong to a circle of superheroes (at least that we know of), they nevertheless strive each day to make the planet a better place.

Welcome to C&EN’s first annual Talented 12 issue, in which we highlight path-paving young researchers and entrepreneurs who are using chemistry to solve global problems. Among other things, this impressive group is seeking ways to synthesize molecules in a more environmentally friendly way, developing methods to curb global warming by removing carbon dioxide from the air, and investigating the biochemical underpinnings of diseases to help find cures.

We selected 12 of them as a nod toward their chemical roots: The International Union of Pure & Applied Chemistry defines the mole—a fundamental unit of measure for chemists—with respect to the number of atoms in 12 g of carbon-12.

Selecting the Talented 12 and putting together this package took months of effort. We called upon a diverse panel of esteemed advisers to recommend nominees. We asked that nominees be chemical scientists who are under the age of 42, are on the verge of becoming leaders, and are challenging the conventional wisdom in their fields. We also sifted through past nominees for the Nobel Laureate Signature Award for Graduate Education in Chemistry, a national prize given each year to an outstanding graduate student by the American Chemical Society. Then we researched our pool of candidates, interviewed their colleagues, and finally, chose our finalists during an intense evaluation session.

You might not recognize the names of the dozen chemists on our list. Their research might not yet be on your radar. But we’re convinced that if we hadn’t put the spotlight on them, their secret identities would have eventually been revealed through their undeniable scientific feats.

 

 

Emily Balskus

The Microbiome Code Breaker

Microbe maven is exploring the chemistry of our bodies’ bacteria

by Bethany Halford

 

Emily Balskus
Credit: Richard C. Smith

The human microbiome is full of mysteries, and Emily P. Balskus is out to solve them. Take the case of trimethylamine. For more than 100 years, scientists had known that bacteria living in our gut convert the essential nutrient choline to trimethylamine. That trimethylamine bacterial by-product has been linked to diseases both common, such as heart disease, and rare, such as the metabolic disorder known as fish malodor syndrome.

Vitals

Current Affiliation: Harvard University

Age: 35

Ph.D. Alma Mater: Harvard University

Talent: Deciphering the chemistry of the human microbiome to understand its role in disease.

Scientific Role Model: Jennifer Doudna. “She’s shown amazing creativity in her work and in her ability to identify difficult problems that are impactful.”

But scientists had no idea about the underlying genetics of this process or which enzyme was cleaving choline’s C–N bond to generate trimethylamine. Balskus, a chemist at Harvard University, decided to track down the biochemical culprit. In 2012, her lab identified the gene cluster responsible for the reaction as well as the glycyl radical enzyme that does the chopping. It turns out that this kind of chemistry had never been seen before from enzymes in this family. Now scientists are wondering if they can target the enzyme to curb heart disease.

When microbiologists began to study the human microbiome, they focused on the kinds of bacteria populating our bodies, Balskus explains. But the real secret to understanding and manipulating the human microbiome isn’t about what these organisms are so much as it is about what they do. By identifying and targeting those biochemical processes, scientists might then begin to manipulate them. “And this,” Balskus says, “presents an enormous opportunity for chemists.”


Three Key Papers

“A Biocompatible Alkene Hydrogenation Merges Organic Synthesis with Microbial Metabolism” (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201403148)

“A Prodrug Mechanism is Involved in Colibactin Biosynthesis and Cytotoxicity” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja312154m)

“Microbial Conversion of Choline to Trimethylamine Requires a Glycyl Radical Enzyme” (Proc. Natl. Acad. Sci. USA 2012, DOI: 10.1073/pnas.1215689109)


Research At A Glance

At Harvard, Balskus and her group are doing detective work on the biochemistry of the human microbiome. They’ve already figured out the enzyme responsible for generating trimethylamine from choline in the gut. Inhibiting this process could curb heart disease.
Credit: Shutterstock/C&EN

At Harvard, Balskus and her group are doing detective work on the biochemistry of the human microbiome. They’ve already figured out the enzyme responsible for generating trimethylamine from choline in the gut. Inhibiting this process could curb heart disease.

 

 

Tobias Erb

The CO2 Wrangler

Chemical biologist is developing enzymatic ways to turn the excess CO2

by Sarah Everts

 

Tobias Erb
Credit: Richard C. Smith

The vast amount of carbon dioxide churning in our atmosphere and warming up the planet has many researchers chasing efficient ways to remove it from the air.

Vitals

Current Affiliation: Max Planck Institute for Terrestrial Microbiology, in Marburg, Germany

Age: 36

Ph.D. Alma Mater: Albert-Ludwigs University Freiburg

Talent: Transforming CO2 into useful carbon-based compounds, such as biofuels, using enzymes.

Scientific Role Model: Fritz Haber and Carl Bosch. Thanks to these scientists, Erb says, humans can industrially carry out two to three times as much nitrogen fixation as bacteria. “Having something like a Haber-Bosch process for pulling CO2 out of the atmosphere would be fabulous.”

“At the moment, the only thing humans can do is dump it in the ground or the ocean. Or we can trap and sequester it,” says Tobias J. Erb, a synthetic biologist at Max Planck Institute for Terrestrial Microbiology, in Marburg, Germany. Erb has a different strategy: Use bacterial enzymes to pull CO2 from the atmosphere and then convert it into useful carbon-based compounds, such as biofuel or polymers.

As a graduate student, Erb nailed the first step in the process by plucking the world’s fastest and most efficient CO2-fixing enzyme from an ancient purple photosynthetic Proteobacteria called Rhodobacter sphaeroides. The enzyme, crotonyl-CoA carboxylase/reductase (CCR), is nearly 100 times as fast at pulling CO2 out of the atmosphere as the enzyme that plants use.

Plants convert CO2 into useful carbon-based compounds by the gigaton each year, but the enzyme responsible for this transformation, called Rubisco, is not only slow, it’s a bit fickle: About 20% of the time, it chooses to fix oxygen instead of CO2.

Since discovering CCR, Erb has been dissecting the way the enzyme extracts CO2 from the air to make the process more efficient. He’s also assembled an orchestra of 15 enzymes that can work in harmony with CCR to produce basic three-carbon compounds. His goal is to get this system working optimally in a test tube, export it to a bacterial or plant cell, and ramp up the variety and usefulness of products it makes.


Three Key Papers

“The Use of Ene Adducts to Study and Engineer Enoyl-Thioester Reductases” (Nature Chem. Biol. 2015, DOI: 10.1038/nchembio.1794)

“Direct Evidence for a Covalent Ene Adduct Intermediate in NAD(P)H-dependent Enzymes” (Nature Chem. Biol 2014, DOI: 10.1038/nchembio.1385)

“Carboxylation Mechanism and Stereochemistry of Crotonyl-Coa Carboxylase/Reductase, a Carboxylating Enoyl-Thioester Reductase” (Proc. Natl. Acad. Sci. USA 2009, DOI: 10.1073/pnas.0903939106)


Research At A Glance

Erb wants to reduce the greenhouse gas CO2 in Earth’s atmosphere with bacterial enzymes and turn it into useful carbon-based compounds. He’s already discovered a CO2-fixing enzyme, called CCR, that can carry out the toughest step: Pull CO2 out of the air and attach it to an organic molecule, crotonyl-CoA. The long-term goal is to build more complicated, useful compounds such as fuel.
Credit: Shutterstock/C&EN

Erb wants to reduce the greenhouse gas CO2 in Earth’s atmosphere with bacterial enzymes and turn it into useful carbon-based compounds. He’s already discovered a CO2-fixing enzyme, called CCR, that can carry out the toughest step: Pull CO2 out of the air and attach it to an organic molecule, crotonyl-CoA. The long-term goal is to build more complicated, useful compounds such as fuel.
Credit: Shutterstock/C&EN

 

 

Karen Havenstrite

The Soothe Seer

Chemical entrepreneur is improving contact lens design

by Jessica Morrison

 

Karen Havenstrite
Credit: Richard C. Smith

Karen L. Havenstrite once considered becoming a professional poker player. She was so good that she even won first place in an online tournament, besting some 3,000 players to win $12,000. But in 2011, the chemical engineer funneled her penchant for risk-taking into improving human health: She launched a company based on a chance encounter in the lab.

Vitals

Current Affiliation: Ocular Dynamics

Age: 31

Ph.D. Alma Mater: Stanford University

Talent: Using her materials science prowess to invent better versions of medical devices.

Scientific Role Model: “All of the people who mentored me.” Havenstrite worked in five different labs as an undergraduate, starting when she was a freshman in college.

At the end of her doctoral studies at Stanford University, where she was studying chemical engineering and stem cell biology, Havenstrite was working in the lab late one night when she stumbled upon two visiting fellows from a biomedical innovation program. They were dissecting rabbit eyes to try to understand dry eye, a common and uncomfortable issue for contact lens wearers.

Normally, our eyes are kept moist by a thin layer of oil secreted by the eyelid. But wearing contact lenses can cause that moisture to evaporate and leave wearers with uncomfortable dry eyes.

The researchers asked Havenstrite if she had any ideas, sparking a collaboration to develop a more comfortable contact lens. In 2011, just months after Havenstrite defended her thesis, the trio launched Ocular Dynamics, a biotech firm that will commercialize their work, with help from QB3, a University of California biotech accelerator. Havenstrite and her cofounders have already negotiated two licensing agreements for the contact lens technology, and they expect to have it on the market later this year.

To further her entrepreneurial ambitions, Havenstrite just finished her M.B.A. at Stanford. When she told QB3 management about her plans to get a business degree while also running a start-up, they initially balked at the idea. “We thought she was a little busy,” quips QB3 Associate Director Douglas Crawford. “But she did both brilliantly.” – Jessica Morrison


Three Key Papers

“Substrate Elasticity Regulates Skeletal Muscle Stem Cell Self-Renewal in Culture” (Science 2010, DOI: 10.1126/science.1191035)

“Contact lens with a hydrophilic layer” (US Patent 2014005574)

“Perturbation of single hematopoietic stem cell fates in artificial niches” (Integrative Biol. 2009, DOI: 10.1039/b815718a)


Research At A Glance

Contact lenses cause natural moisture—our tears—to evaporate, leading to uncomfortable dry eye for some wearers. Havenstrite and her partners have developed a lens coating (purple) that helps retain moisture (blue) as well as lipids (yellow) secreted by the eyelid, thereby helping to treat dry eye.
Credit: Ocular Dynamics/C&EN

Contact lenses cause natural moisture—our tears—to evaporate, leading to uncomfortable dry eye for some wearers. Havenstrite and her partners have developed a lens coating (purple) that helps retain moisture (blue) as well as lipids (yellow) secreted by the eyelid, thereby helping to treat dry eye.

 

 

Jacob Hooker

The Mind Mapper

Radiochemist makes probes for studying chemical dysfunction in the brain

by Ryan Cross

 

Jacob Hooker
Credit: Richard C. Smith

Attendees at Jacob M. Hooker’s group meetings should be prepared for a head-spinning sampling of science. In a single meeting they’re as likely to discuss palladium, and the role it plays as a catalyst for constructing compounds, as they are to talk about the pallidum, a part of the brain that’s involved in behavior, emotions, and addiction.

Vitals

Current Affiliation: Harvard Medical School and the Athinoula A. Martinos Center for Biomedical Imaging at Massachusetts General Hospital

Age: 35

Ph.D. Alma Mater: University of California, Berkeley

Talent: Dreaming up new radiolabeled molecules that provide insight into the brain’s activity.

Scientific Role Model: Joanna S. Fowler. “She continues throughout her career to redefine herself and excel in so many ways. And it’s not just the science. She always puts people first. She taught me that science is made of individuals working together to accomplish goals.”

Hooker, a radiochemist at Harvard Medical School, leads a team that designs and makes radiolabeled compounds for positron emission tomography and then uses them to study the brain. “What unifies us is the fact that I’m a chemist and think about things from a molecular basis,” Hooker says.

Last year Hooker and colleagues began their first human studies of a compound they designed from scratch—known as [11C]Martinostat. The radiotracer binds to histone deacetylases, enzymes that are important for DNA expression. Hooker hopes it will shed light on changes in the brain that occur as a result of aging, psychiatric, and neurodegenerative diseases and may help scientists as they design drugs to treat those diseases.

Being able to see his work through to the application stage has always been important to Hooker. Only after hearing a talk about the chemistry behind color, polymer science, and textiles as a high school student did Hooker decide on a career path, ultimately earning an undergraduate degree in textile chemistry. On paper it seems an unlikely start for someone in chemical neuroscience. But to Hooker it’s a completely logical beginning. Walking the line between pure and applied science, he says, has come to define what he does.


Three Key Papers

“Evidence of Brain Glial Activation in Chronic Pain Patients” (Brain 2015, DOI: 10.1093/brain/awu377)

“In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs” (J. Med. Chem. 2014, DOI: 10.1021/jm500872p)

“A Fluoride-derived Electrophilic Late-Stage Fluorination Reagent for PET Imaging” (Science 2011, DOI: 10.1126/science.1212625)


Research At A Glance

Hooker creates radiolabeled molecules that help researchers study changes in the brain at the molecular level. This positron emission tomography brain map was made with [11C]Martinostat, a molecule that binds to histone deacetylases. The highest concentrations of the molecule are red, the lowest are blue.
[11C]Martinostat, a molecule that binds to histone deacetylases
Credit: Jacob Hooker

Hooker creates radiolabeled molecules that help researchers study changes in the brain at the molecular level. This positron emission tomography brain map was made with [11C]Martinostat, a molecule that binds to histone deacetylases. The highest concentrations of the molecule are red, the lowest are blue.

 

 

Kami Hull

The Green Aminator

Synthesis innovator is developing greener, more efficient methods for modifying molecules

by Sarah Everts

 

Kami Hull
Credit: Richard C. Smith

Kami L. Hull likes to build stuff. She began an undergraduate degree in theater set design but later got hooked on molecular-scale construction. “I saw the beauty in building very small scaffolds, and I thought, ‘I could apply my skills from the theater world to chemistry.’ ”

Vitals

Current Affiliation: University of Illinois, Urbana-Champaign

Age: 34

Ph.D. Alma Mater: University of Michigan, Ann Arbor

Talent: Devising more environmentally friendly synthesis routes for installing chemical groups in molecular scaffolds.

Scientific Role Model: Marie Curie. “Despite the fact that she was unable to enroll in a standard university because of her gender and the fact that she was poor, she sought out an education and self-financed it. Looking back at my own education and career, and reading about hers, I realize how lucky I was to be born in 1980 rather than in 1880.”

Specifically, she’s designing faster and more efficient ways to make important molecules—such as pharmaceuticals—with methods that also conserve our dwindling natural resources.

When she started her own lab at the University of Illinois, Urbana-Champaign, three years ago, Hull took a long look at a poster showing the world’s top 100 drug molecules. “More than 90% of these molecules have some sort of nitrogen atom in them,” she says. The way chemists add a nitrogen-hydrogen group across two carbon atoms—a so-called hydroamination—is very wasteful, she adds. These reactions often require many steps, an excessive amount of solvent, and reagents that aren’t environmentally friendly. Her current mission is to find green ways to install nitrogen groups in organic molecules while controlling the overall chirality, or handedness, of the molecule.

Her track record suggests she’ll be successful. As a Ph.D. student in Melanie Sanford’s group at the University of Michigan, Ann Arbor, Hull helped popularize palladium acetate as a workhorse catalyst for replacing the hydrogens in a carbon-hydrogen bond with everything from fluorine to complex carbon-ring structures. “Everyone uses this palladium catalyst so much that it has become dogma,” says David Thaisrivongs, a process chemist at Merck & Co. Now that the catalyst has become ubiquitous, “people take it for granted.”


Three Key Papers

“Regio- and Chemoselective Intermolecular Hydroamination of Allyl Imines for the Synthesis of 1,2-Diamines” (J. Am. Chem. Soc. 2014, DOI: 10.1021/ja505794u)

“Palladium-Catalyzed Fluorination of Carbon-Hydrogen Bonds” (J. Am. Chem. Soc. 2006, DOI: 10.1021/ja061943k)

“A Highly Selective Catalytic Method for the Oxidative Functionalization of C−H Bonds” (J. Am. Chem. Soc. 2004, DOI: 10.1126/10.1021/ja031543m)


Research At A Glance

During grad school, Hull helped develop a palladium catalyst that, under various conditions, could functionalize C–H bonds in molecules with fluorines, aryls, and other groups.

During grad school, Hull helped develop a palladium catalyst that, under various conditions, could functionalize C–H bonds in molecules with fluorines, aryls, and other groups.

 

 

Matt Kanan

The Renewable Energy Reaper

Jack of all trades is catalytically converting CO2 into fuels and chemical building blocks

by Jessica Morrison

 

Matt Kanan
Credit: Richard C. Smith

Most chemists would be satisfied with making a major contribution to one field of research. Matthew W. Kanan has already made discoveries in three fields and counting: As a graduate student, he helped pioneer DNA-templated organic synthesis, a molecule-building technique that uses DNA strands to bring reactants together. As a postdoc, he discovered a game-changing catalyst for splitting water and generating hydrogen fuel. And now as a team leader, he’s finding ways of turning the greenhouse gas CO2 into useful materials

Vitals

Current Affiliation: Stanford University

Age: 37

Ph.D. Alma Mater: Harvard University

Talent: Finding ways of converting bountiful molecules, such as H2O, CO2, and N2, into sustainable fuels and chemical building blocks.

Scientific Role Model: None. “I’m averse to the concept. I admire many people’s work … in science there is no one model for success. There are as many successful models as there are successful scientists.”

“Lightning doesn’t strike in the same place three times by accident,” says Martin D. Burke, an organic chemist at the University of Illinois, Urbana-Champaign (UIUC). Burke says that he tried to recruit Kanan to UIUC but that he lost out when Kanan ultimately chose to start his own lab at Stanford University.

To Kanan, tackling new fields of research isn’t daunting—it’s just part of who he is. “I have this hybrid background,” Kanan says. “Some people bend their expertise to fit a problem. I like to think of myself the other way.” Kanan says he goes after grand challenges whether he has the background or not.

Kanan’s now trying to solve the problem of Earth’s dwindling fossil fuels by gaining expertise in CO2 recycling. “Our overall goal is to make it possible and viable to recycle carbon dioxide into commodity chemicals and fuels,” he says. To achieve that objective, Kanan and his team are studying crystalline grain boundaries in solid catalysts, such as copper and gold, to optimize their ability to convert CO2 into ethanol.


Three Key Papers

“Electroreduction of Carbon Monoxide to Liquid Fuel on Oxide-Derived Nanocrystalline Copper” (Nature 2014, DOI: 10.1038/nature13249)

“In Situ Formation of an Oxygen-Evolving Catalyst in Neutral Water Containing Phosphate and Co2+” (Science 2008, DOI: 10.1126/science.1162018)

“Reaction Discovery Enabled by DNA-templated Synthesis and In Vitro Selection” (Nature 2004, DOI: 10.1038/nature02920)


Research At A Glance

To turn CO2, a climate change culprit, into something useful, Kanan and his team are investigating solid catalysts such as copper (shown here, about 10 nm in diameter). They hope to efficiently convert the gas into ethanol and other chemicals.

To turn CO2, a climate change culprit, into something useful, Kanan and his team are investigating solid catalysts such as copper (shown here, about 10 nm in diameter). They hope to efficiently convert the gas into ethanol and other chemicals.

 

 

Luke Lavis

The Fluorescence Phenom

Molecular designer dreams up dyes that let researchers map molecules inside cells

by Melody M. Bomgardner

 

Luke Lavis
Credit: Richard C. Smith

As a student, Luke D. Lavis was seduced by the beauty and logic of organic chemistry. But his four years in industry before graduate school convinced him that when it comes to job satisfaction, happy customers win out over elegant syntheses. Now he designs and makes complex molecular probes—tools without which biologists couldn’t peer inside cells and neurons.

Vitals

Current Affiliation: Janelia Research Campus, Howard Hughes Medical Institute

Age: 38

Ph.D. Alma Mater: University of Wisconsin, Madison

Talent: Designing dyes to track molecules in living cells.

Scientific Role Model: Linus Pauling, a fellow Oregonian. “He really showcased how simple intuition can lead us on the right path to discover new things.”

“You know when your compounds are working. If people are willing to part with their money or time to test them, that’s when you’ve got something interesting,” Lavis says.

Lavis designs fluorescent dyes that allow researchers to watch, in real time, how biochemicals flow into and behave in live cells. Tagged molecules, such as proteins, can be programmed to glow in the presence of light, enzymes, or other environmental changes. His colleagues at the Janelia Research Campus of Howard Hughes Medical Institute rely on his work to make groundbreaking discoveries.

“I sometimes call Luke our secret weapon here,” says Eric Betzig, a coworker and 2014 Chemistry Nobel Prize recipient. “Every advance I’ve made in my career has been due to fluorescent probes.” Betzig explains that his work developing superresolution microscopy requires dyes that are incredibly bright, long lasting, and available in multiple colors.

Other happy customers include scientists at the roughly 30 Janelia labs in the Transcription Imaging Consortium. Lavis’s dyes let researchers observe the intricate activity of transcription factors, proteins that control gene expression in various cells by translating DNA into RNA. Until now, it has not been possible to observe transcription factors in action—they find their target then disperse in a fraction of a second.


Three Key Papers

“A General Method To Improve Fluorophores for Live-Cell And Single Molecule Microscopy” (Nat. Methods 2015, DOI: 10.1038/nmeth.3256)

“3-D Imaging Of Sox2 Enhancer Clusters in Embryonic Stem Cells” (eLife 2014, DOI: 10.7554/elife.04236.001)

“Synthesis of Rhodamines from Fluoresceins Using Pd-Catalyzed C–N Cross-Coupling” (Org. Lett. 2011, DOI: 10.1021/ol202618tu)


Research At A Glance

Cell biologists would like to track the movement of individual molecules inside living cells using fluorescence microscopy. At Janelia Research Campus, Lavis designs innovative dyes that bind to specific molecules in cells. Two such dyes are shown here; one is bound inside a cell to a transcription factor (TetR, blue), and the other is bound to a histone protein (red).
Credit: Brian English, Luke Lavis & Jiji Chen/Janelia Research Campus/HHMI

Cell biologists would like to track the movement of individual molecules inside living cells using fluorescence microscopy. At Janelia Research Campus, Lavis designs innovative dyes that bind to specific molecules in cells. Two such dyes are shown here; one is bound inside a cell to a transcription factor (TetR, blue), and the other is bound to a histone protein (red).

 

 

Troy Lister

The Bug Battler

Medicinal chemist takes unconventional approach to battling bacteria

by Lisa M. Jarvis

 

Troy Lister
Credit: Richard C. Smith

As a boy in Australia, Troy Lister always liked building things—intricate model airplanes or complex electronic circuits—and knew he’d end up working with his hands. Today, his tinkering might be on the microscopic scale, but its impact is definitely bigger. Lister is trying to construct molecules that could stop our worst bacterial nightmare.

Vitals

Current Affiliation: Spero Therapeutics

Age: 35

Ph.D. Alma Mater: Flinders University, Adelaide, Australia

Talent: Developing molecules to weaken bacterial defenses.

Scientific Role Model: Richard Feynman. The quote that made him most want to emulate Feynman? “Study hard what interests you the most in the most undisciplined, irreverent, and original manner possible.”

In the past 50 years, only two new classes of antibiotics have made it onto the market—every other “novel” microbe killer has come from tweaking older molecules. So swiftly are bacteria outwitting us that, in 2014, the World Health Organization warned we were on the verge of a post-antibiotic world.

Lister is trying to prevent that nightmare scenario in a rather unconventional way.

As head of chemistry at the tiny Cambridge, Mass.-based start-up Spero Therapeutics, Lister isn’t designing compounds that directly kill bacteria. Instead, Spero’s molecules weaken bacterial defenses so that infections are less aggressive and older antibiotics can be used at lower doses to completely knock them out.

The most advanced compounds hobble the highly polar outer membrane used by gram-negative bacteria to repel large, lipid-loving antibiotics. Another effort targets a signaling protein that disarms Pseudomonas aeruginosa, making it easier for the immune system or an antibiotic to clear the infection.

Few companies have been willing to chase molecules that fall outside the traditional antibiotic paradigm. “It’s a much tougher concept to understand clinically and to develop drugs for,” Lister says. “But you’re not going to significantly advance the field if you’re only making incremental improvements over what’s out there.”


Three Key Papers

“Design, Synthesis, and Biological Evaluation of Platensimycin Analogues with Varying Degrees of Molecular Complexity” (J. Am. Chem. Soc. 2008, DOI: 10.1021/ja8044376)

“Cascade Reactions Involving Formal [2+2] Thermal Cycloadditions: Total Synthesis of Artochamins F, H, I, and J” (Angew. Chem. Int. Ed. 2007, DOI: 10.1002/anie.200702363)

“Total Synthesis of Auripyrone A” (Angew. Chem. Int. Ed. 2006, DOI: 10.1002/anie.200504573)


Research At A Glance

A tough-to-penetrate outer membrane has made it nearly impossible for chemists to find new classes of drugs to combat gram-negative bacteria. As head of chemistry at Spero Therapeutics, Lister is working on molecules called potentiators, which weaken that highly polar barrier, allowing traditional antibiotics to sneak in and do their killing.
Credit: CDC/Spero Therapeutics/C&EN

A tough-to-penetrate outer membrane has made it nearly impossible for chemists to find new classes of drugs to combat gram-negative bacteria. As head of chemistry at Spero Therapeutics, Lister is working on molecules called potentiators, which weaken that highly polar barrier, allowing traditional antibiotics to sneak in and do their killing.

 

 

Matt MacDonald

The Oxidation Agent

Organosilicon chemist creates molecules to help shrink electronics

by Matt Davenport

 

Matt MacDonald
Credit: Richard C. Smith

Matthew R. MacDonald came into graduate school feeling like he had something to prove. With no undergraduate research experience, he knew he would have to work overtime just to keep up with his peers in the lab of prominent organometallic chemist William J. Evans at the University of California, Irvine.

Vitals

Current Affiliation: Air Products & Chemicals

Age: 29

Ph.D. Alma Mater: University of California, Irvine

Talent: Pushing chemists’ understanding of what electrons can do in molecules and what molecules can do for electronics.

Scientific Role Model: Thomas Edison. MacDonald says Edison taught him that the road to success is paved with patience, persistence, and failure.

What MacDonald didn’t know was that, in the process of proving himself, he would also prove a few things about fundamental chemistry. By the time he graduated in 2013, MacDonald had discovered new oxidation states for eight elements, shaking up long-held chemical beliefs.

Chemists did not think that these states could exist in molecules, Evans says. MacDonald’s doctoral work is a reminder that “we’re not as mature as we thought we were in chemistry,” Evans adds.

This reminder came, in part, thanks to MacDonald’s deep scientific curiosity. The soft-spoken, Southern Californian surfer says he rarely takes anything as a given. That’s why he bothered looking into the oxidation states that were assumed to be understood.

MacDonald now works for Air Products & Chemicals, where he’s developing volatile precursors that will allow microelectronics companies to create smaller silicon components for their ever-shrinking products.

Some experts predict it’s just a matter of time before companies are unable to cram any more processing power into smaller devices like smartphones. MacDonald and Air Products are working to help the microelectronics industry reach that limit, but perhaps it wouldn’t be surprising if MacDonald challenges a few more scientific assumptions along the way.


Three Key Papers

“Completing the Series of +2 Ions for the Lanthanide Elements: Synthesis of Molecular Complexes of Pr2+, Gd2+, Tb2+, and Lu2+” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja403753j)

“Identification of the +2 Oxidation State for Uranium in a Crystalline Molecular Complex, [K(2.2.2-Cryptand)][(C5H4SiMe3)3 U]” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja406791t)

“Expanding Rare-Earth Oxidation State Chemistry to Molecular Complexes of Holmium(II) and Erbium(II)” (J. Am. Chem. Soc. 2012, DOI: 10.1021/ja303357w)


Research At A Glance

Challenging conventional wisdom about the periodic table, MacDonald discovered new oxidation states for eight of its members (highlighted), many of which are rare-earth elements. A complex that he created with uranium in the +2 oxidation state is shown.
Credit: J. Am. Chem. Soc.

Challenging conventional wisdom about the periodic table, MacDonald discovered new oxidation states for eight of its members (highlighted), many of which are rare-earth elements. A complex that he created with uranium in the +2 oxidation state is shown.

 

 

Denis Malyshev

The DNA Amplifier

Synthetic biologist is expanding the genetic alphabet to create unnatural proteins

by Melody M. Bomgardner

 

Denis Malyshev
Credit: Richard C. Smith

Earthly life-forms, from microbes to whales, all share the same DNA structure, with ladder rungs that pair the amino acids adenine with thymine and cytosine with guanine. Or at least they did until 2014, when grad student Denis Malyshev and colleagues at Scripps Research Institute California revealed they had inserted functional DNA, expanded with a third, man-made base pair, into living Escherichia coli bacteria.

Vitals

Current Affiliation: Synthorx

Age: 29

Ph.D. Alma Mater: Scripps Research Institute California

Talent: Engineering DNA with unnatural base pairs and inserting it into living cells to make never-before-seen proteins.

Scientific Role Model: Elon Musk. He challenges conventional wisdom, goes against the flow, and backs his ideas with his own money, Malyshev says.

Synthetic biologists manipulate the genes of bacteria every day, but they are limited to using nature’s four-letter DNA alphabet. By giving bacteria more letters to work with, Malyshev and his colleagues greatly expanded the number of products they can manufacture.

Malyshev, who grew up in Russia, began his scientific training very young; he attended a chemistry-focused high school in Moscow that emphasized research. As an undergraduate at the Higher Chemical College of the Russian Academy of Sciences, Malyshev was a coauthor on eight research articles, including one in the Journal of the American Chemical Society.

At Scripps, Malyshev landed in the lab of Floyd E. Romesberg, whose team was working with man-made nucleotides. “I was so thrilled with the idea of tinkering with the most important thing in nature,” Malyshev recalls.

Malyshev coaxed the expanded DNA into replicating in a polymerase chain reaction. But it was his work in living cells that brought worldwide attention to the research. He created the first semisynthetic organism, with a six-letter genetic alphabet and the potential to make entirely new types of proteins.

Malyshev is now a scientist at La Jolla, Calif.-based Synthorx, a start-up founded by Romesberg to translate the potential of those unnatural proteins into actual products. “I want to see this impact biotechnology, drug discovery, and vaccine development,” Malyshev says. “We have a chance to disrupt how medical biology is done today.”


Three Key Papers

“A Semi-Synthetic Organism with an Expanded Genetic Alphabet” (Nature 2014, DOI:10.1038/nature13314)

“PCR with an Expanded Genetic Alphabet” (J. Am. Chem. Soc. 2009, DOI: 10.1021/ja906186f)

“Palladium and Platinum Catalyzed Hydroselenation of Alkynes: Se–H vs SE–SE Addition to C=C Bond” (J. Organomet. Chem. 2003, DOI: 10.1016/s0022-328x(03)00546-1)


Research At A Glance

As a grad student, Malyshev added a man-made base pair (X-Y, shown) to DNA and then inserted the genetic material into living bacteria. The work opens the possibility of building never-before-seen proteins with novel amino acids.
Credit: Synthorx

As a grad student, Malyshev added a man-made base pair (X-Y, shown) to DNA and then inserted the genetic material into living bacteria. The work opens the possibility of building never-before-seen proteins with novel amino acids.

 

 

Hosea Nelson

The Bioactives Builder

Organic chemist is finding new synthetic routes to Mother Nature’s molecules

by Lisa M. Jarvis

 

Hosea Nelson
Credit: Richard C. Smith

Hosea M. Nelson never planned on becoming a scientist. In fact, he was on his way to becoming a sheet metal worker when a particularly unpleasant foreman made him realize he’d be happiest as his own boss. He quit and enrolled in community college, with vague aspirations of going into psychology. One chemistry class later, his fate was sealed.

Vitals

Current Affiliation: UCLA

Age: 37

Ph.D. Alma Mater: California Institute of Technology

Talent: Tackling complex syntheses of medicinally relevant natural products and devising novel, economical catalysts.

Scientific Role Model: Percy Julian. “Any difficulty or challenge associated with being an underrepresented minority today pales in comparison to what Percy Julian went through in Alabama.”

That independent streak made Nelson an early standout in graduate school at California Institute of Technology. After joining Brian Stoltz’s lab there, Nelson completed the total synthesis of a class of medicinally relevant molecules derived from Thapsia, a plant more commonly known as the “deadly carrot.” Although most students take a few years to fully take charge of their research projects, Nelson jumped headlong into his thesis, impressing Stoltz with his creativity. “I loved talking chemistry with him. He would show me what he wanted to do, and I would just help him do it,” Stoltz says. “He clearly had a plan from the beginning.”

Earlier this month, Nelson finally became his own boss. The doors to his labs at the University of California, Los Angeles, opened on July 1. And he’s got big ideas about the kind of science his research group will do.

Ultimately, he wants to combine multiple types of chemistry to mimic what nature does best: make complex, bioactive molecules. One day, Nelson imagines, “you could just have a flask filled with starting materials and then design, computationally, some set of catalysts to push it toward a product.”

A lofty goal, but one he seems fully capable of realizing. “I think he’s going to set the world on fire,” Stoltz says.


Three Key Papers

“Enantioselective 1,1-Arylborylation of Alkenes: Merging Chiral Anion Phase Transfer with Pd Catalysis” (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b00344)

“Total Syntheses of (−)-Transtaganolide A, (+)-Transtaganolide B, (+)-Transtaganolide C, and (−)-Transtaganolide D and Biosynthetic Implications” (Angew. Chem. Int. Ed. 2013, DOI: 10.1002/anie.201301212)

“Selective Nucleic Acid Capture with Shielded Covalent Probes” (J. Am. Chem. Soc. 2013, DOI: 10.1021/ja4009216)


Research At A Glance

The medicinal properties of plants from the genus Thapsia, more commonly known as the “deadly carrot” (shown), have been known for centuries. As a grad student at Caltech, Nelson worked out an elegant five-step synthesis of the transtaganolides, a family of compounds isolated from Thapsia. The natural products could be useful in treating malaria, African sleeping sickness, and certain cancers. The medicinal properties of plants from the genus Thapsia, more commonly known as the “deadly carrot” (shown), have been known for centuries. As a grad student at Caltech, Nelson worked out an elegant five-step synthesis of the transtaganolides, a family of compounds isolated from Thapsia. The natural products could be useful in treating malaria, African sleeping sickness, and certain cancers.
Credit: Nelson/C&EN

The medicinal properties of plants from the genus Thapsia, more commonly known as the “deadly carrot” (shown), have been known for centuries. As a grad student at Caltech, Nelson worked out an elegant five-step synthesis of the transtaganolides, a family of compounds isolated from Thapsia. The natural products could be useful in treating malaria, African sleeping sickness, and certain cancers.

 

 

Brad Olsen

The Macromolecule Melder

Materials maverick is powering up polymers by joining them with proteins

by Matt Davenport

 

Brad Olsen
Credit: Richard C. Smith

Materials science maven Paula T. Hammond had an inkling that there was something different about Bradley D. Olsen when he was a sophomore at Massachusetts Institute of Technology. He was sharp and curious to the point of distinction.

Vitals

Current Affiliation: MIT

Age: 34

Ph.D. Alma Mater: University of California, Berkeley

Talent: Creating polymers with unique blends of bioactivity and material properties.

Scientific Role Model: Polymer pioneers Paul Flory and Pierre-Gilles de Gennes and materials scientist Edward Kramer. “All of these people have had an influence on my approach to scientific research.”

She and her colleagues knew they should keep an eye on Olsen after he left Cambridge, Mass., in 2003. He made that task a lot easier by joining MIT’s faculty in 2009.

Olsen’s team is now bridging the fields of biochemistry and polymer design by incorporating proteins into self-assembling block copolymers. Beyond boasting novel material characteristics, the resulting polymers can have unique bioactive properties.

The team’s hybrid materials could have applications in detoxifying chemical spills, stemming blood loss from wounds, and even repairing amniotic sacs to help extend pregnancies at risk of ending early. “His materials take on everything, from our core chemical sensibilities to helping human health,” Hammond reflects.

Olsen is already drawing comparisons to the likes of iconic interdisciplinary researchers George M. Whitesides and Samuel I. Stupp for his ability to ask powerful questions and his fearlessness when it comes to answering them. DuPont recently named him to its 2015 class of young professors.

Olsen is quick to attribute his dauntless approach to science to all those who have helped him, including his research group. “There’s a predisposition to intellectual curiosity, sure,” he tells C&EN. “But it comes from working with great mentors.”


Three Key Papers

“Anomalous Self-Diffusion and Sticky Rouse Dynamics in Associative Protein Hydrogels” (J. Am. Chem. Soc. 2015, DOI: 10.1021/jacs.5b00722)

“Artificially Engineered Protein Hydrogels Adapted from the Nucleoporin Nsp1 for Selective Biomolecular Transport” (Adv. Mater. 2015, DOI:
10.1002/adma.201500752)

“Solid-State Nanostructured Materials from Self-Assembly of a Globular Protein-Polymer Diblock Copolymer” (ACS Nano 2011, DOI: 10.1021/nn2013673)


Research At A Glance

By incorporating proteins (red) into synthetic polymers (blue), Olsen’s group at MIT is creating a class of biomaterials with potential in many applications, including injectable implants.
Credit: ACS Nano/Biomacromolecules

By incorporating proteins (red) into synthetic polymers (blue), Olsen’s group at MIT is creating a class of biomaterials with potential in many applications, including injectable implants.


Our Advisers:

Bruce Booth, a partner at life science and technology investment firm Atlas Venture; Martin D. Burke, an organic chemist at the University of Illinois, Urbana-Champaign; Douglas Crawford, a managing director at bioscience investment firm Mission Bay Capital; Paula T. Hammond, a chemical engineer at Massachusetts Institute of Technology; Laura L. Kiessling, a biochemist at the University of Wisconsin, Madison; Jay Lichter , a biotech investor at Avalon Ventures; Craig W. Lindsley , a medicinal chemist at Vanderbilt University; Timothy M. Swager, a materials and analytical chemist at MIT; Christopher Welch, a process and analytical chemist at Merck & Co.; and Helma Wennemers, an organic chemist at the Swiss Federal Institute of Technology (ETH), Zurich.


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