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“Designing electrolytes to control electrochemical processes”

Chibueze Amanchukwu

“Maximizing CO2 capture in photosynthetic organisms”

Ahmed Badran

“Using abundant materials to make safer batteries”

Rachel Carter

“Driving enhanced tire sustainability and performance”

Rob Dennis-Pelcher

“Developing electrochemical tools to understand corrosion”

Samantha M. Gateman

“Therapeutically targeting structurally dynamic RNAs”

Alisha Jones

“Harnessing radiochemistry to investigate environmental pollutants”

Outi Keinänen

“Developing new approaches to oligonucleotide manufacturing”

Sarah Lovelock

Nominate for the T12 class of 2025

Nominations

“A path toward drugging the ‘undruggable’ ”

Jesus Moreno

“Innovating nanoscale biosensors for human health”

Nako Nakatsuka

“Discovering unknown metabolites with chemical AI”

Michael Skinnider

“Radical catalysis for sustainable synthesis”

Julian West

Register for the T12 Symposium

T12 Symposium

“Designing electrolytes to control electrochemical processes”

Chibueze Amanchukwu

“Maximizing CO2 capture in photosynthetic organisms”

Ahmed Badran

“Using abundant materials to make safer batteries”

Rachel Carter

“Driving enhanced tire sustainability and performance”

Rob Dennis-Pelcher

“Developing electrochemical tools to understand corrosion”

Samantha M. Gateman

“Therapeutically targeting structurally dynamic RNAs”

Alisha Jones

“Harnessing radiochemistry to investigate environmental pollutants”

Outi Keinänen

“Developing new approaches to oligonucleotide manufacturing”

Sarah Lovelock

“A path toward drugging the ‘undruggable’ ”

Jesus Moreno

“Innovating nanoscale biosensors for human health”

Nako Nakatsuka

“Discovering unknown metabolites with chemical AI”

Michael Skinnider

“Radical catalysis for sustainable synthesis”

Julian West

Nominate for the T12 class of 2025

Nominations

Register for the T12 Symposium

T12 Symposium

“Designing electrolytes to control electrochemical processes”

Chibueze Amanchukwu

“Maximizing CO2 capture in photosynthetic organisms”

Ahmed Badran

“Using abundant materials to make safer batteries”

Rachel Carter

“Driving enhanced tire sustainability and performance”

Rob Dennis-Pelcher

“Developing electrochemical tools to understand corrosion”

Samantha M. Gateman

“Therapeutically targeting structurally dynamic RNAs”

Alisha Jones

“Harnessing radiochemistry to investigate environmental pollutants”

Outi Keinänen

“Developing new approaches to oligonucleotide manufacturing”

Sarah Lovelock

“A path toward drugging the ‘undruggable’ ”

Jesus Moreno

“Innovating nanoscale biosensors for human health”

Nako Nakatsuka

“Discovering unknown metabolites with chemical AI”

Michael Skinnider

“Radical catalysis for sustainable synthesis”

Julian West

Nominate for the T12 class of 2025

Nominations

Register for the T12 Symposium

T12 Symposium
NMR tube icon
NMR spectrometer icon
Structured RNA icon
Structured RNA icon
NMR spectrometer icon
Headshot of Alisha Jones Headshot of Alisha Jones
Credit: Hailee Williams
May 17, 2024 | A version of this story appeared in Volume 102, Issue 15
Structural Biology
“Therapeutically
targeting
structurally
dynamic RNAs”
Alisha  Jones

Hearing her full name yelled through the house, a young Alisha Jones—Jonesy to nearly everyone—knew she was in trouble. Inspired by a chemistry class, Jones had started experimenting with bathroom supplies, mixing them together and looking for a reaction. She stored premixed concoctions in old hair care containers and hid them at the back of her closet to pull out for science demos with friends. Her mother had just stumbled upon the containers and inadvertently used one. “Basically, she put bleach in her hair,” Jones says. “Very powerful bleach.”

Vitals

Current affiliation: New York University

Age: 36

PhD alma mater: University of Washington

Hometown: West Haven, Connecticut, and Toledo, Ohio

If I were an element, I’d be: “Magnesium. We already know that many enzymes rely on it to function, but have you seen what that ion does to RNA structure?”

My role models are: “My mom and dad. I’ve learned from them how to persevere—when things aren’t the most ideal, sometimes you just have to get creative and come up with alternate ways to make things work. They’ve taught me that sometimes you just have to go and do your own thing. . . . Don’t worry about what everyone else is doing. You do you; there’s beauty, happiness, and success in that.”

Luckily, a trip to the salon remedied the error, and this first hard lesson on the importance of clear chemical labeling didn’t scare Jones, or her family, away from chemistry. In fact, she says her parents encouraged her to pursue science. Now Jones runs her own lab at New York University, where she combines traditional experimental methods with computational modeling to determine how long, dynamic RNA strands control different cellular processes.

According to biology’s central dogma, RNA has one main function: coding for the synthesis of proteins. But that’s not the whole picture. In fact, researchers now know many RNAs are noncoding—they don’t get translated into proteins.

Jones is fascinated by these RNAs, specifically long noncoding RNAs (lncRNAs)—those with hundreds or thousands of bases. Some lncRNAs can act like lassos, tethering chromosomes together in the nucleus. Others bind to proteins to protect them from degradation. “You could even have one single RNA that literally regulates six different biological processes,” Jones says.

lncRNAs can play different roles in a cell thanks to their ability to readily change conformations, a process that alters what molecules they can bind to. To better understand the biochemistry of lncRNAs, scientists need to better characterize all these structures. But determining the structure of a lncRNA is no easy task. “We know a lot about protein structures, but we know relatively little about RNA structure,” says Michael Summers, a biochemist at the University of Maryland, Baltimore County, and one of Jones’s colleagues in the field.

While the inherent flexibility of RNA enables it to take on many shapes, and subsequently functions, that flexibility also makes it challenging to crystallize and study with X-ray crystallography or cryo-electron microscopy, the standard approaches to studying protein structure. Many researchers use nuclear magnetic resonance spectroscopy to determine RNA structure. Unfortunately, Jones says, NMR is more effective for short strands of RNA, not lncRNAs. So Jones chops them up.

She and her team deploy a combination of molecular biology techniques that allow them to clip a lncRNA into structured regions that fold independently of the parent strand. Then the scientists can use NMR to determine the 3D structures of those smaller pieces. The lab’s computational modeling programs can join those smaller 3D structures into a larger structure of the lncRNA, allowing the scientists to start to understand how the RNAs move through different conformations.

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Some of those lncRNA conformations are associated with disease states. “The ultimate goal is to identify a structured state that we can block with some sort of therapeutic agent,” Jones says.

As Jones pursues this goal, she also works to provide high school students from economically disadvantaged or other underrepresented groups with hands-on research opportunities in her laboratory. Despite an early interest in science, Jones says, she didn’t have anyone teaching her what it meant to be a scientist until high school, when she started working in a structural biology lab at the University of Toledo.

Now she has designed her own program to teach high schoolers lab skills. Last year, Jones published a preprint of their work—one that hasn’t gone through peer review—on determining how a specific RNA-binding protein interacts with lncRNAs. “I had three students who worked on a project with me last summer,” she says, “and they’re right in the author list with the PhD students.”

Jones’s aptitude for teaching was evident to her postdoctoral adviser, Michael Sattler, a biochemist at the Technical University of Munich. He recalls Jones as both a passionate scientist and an effective teacher. After Jones completed her postdoc, Sattler wasn’t sure the other students would be able to independently run the experiments Jones had worked on. But it was needless to worry. He was impressed by the skills she’d passed on to them. Ultimately, he suspects that Jones is bound to be an enthusiastic and skilled leader in her field.

Structural Biology

Alisha Jones

This biophysical chemist pairs computational and experimental tools to unravel RNA structure

by Fionna Samuels
May 17, 2024 | A version of this story appeared in Volume 102, Issue 15
Headshot of Alisha Jones smiling.

Credit: Hailee Williams/C&EN | Alisha Jones

 

Vitals

Current affiliation: New York University

Age: 36

PhD alma mater: University of Washington

Hometowns: West Haven, Connecticut, and Toledo, Ohio

If I were an element, I’d be: “Magnesium. We already know that many enzymes rely on it to function, but have you seen what that ion does to RNA structure?”

My role models are: “My mom and dad. I’ve learned from them how to persevere—when things aren’t the most ideal, sometimes you just have to get creative and come up with alternate ways to make things work. They’ve taught me that sometimes you just have to go and do your own thing. . . . Don’t worry about what everyone else is doing. You do you; there’s beauty, happiness, and success in that.”

Hearing her full name yelled through the house, a young Alisha Jones—Jonesy to nearly everyone—knew she was in trouble. Inspired by a chemistry class, Jones had started experimenting with bathroom supplies, mixing them together and looking for a reaction. She stored premixed concoctions in old hair care containers and hid them at the back of her closet to pull out for science demos with friends. Her mother had just stumbled upon the containers and inadvertently used one. “Basically, she put bleach in her hair,” Jones says. “Very powerful bleach.”

Luckily, a trip to the salon remedied the error, and this first hard lesson on the importance of clear chemical labeling didn’t scare Jones, or her family, away from chemistry. In fact, she says her parents encouraged her to pursue science. Now Jones runs her own lab at New York University, where she combines traditional experimental methods with computational modeling to determine how long, dynamic RNA strands control different cellular processes.

According to biology’s central dogma, RNA has one main function: coding for the synthesis of proteins. But that’s not the whole picture. In fact, researchers now know many RNAs are noncoding—they don’t get translated into proteins.

Jones is fascinated by these RNAs, specifically long noncoding RNAs (lncRNAs)—those with hundreds or thousands of bases. Some lncRNAs can act like lassos, tethering chromosomes together in the nucleus. Others bind to proteins to protect them from degradation. “You could even have one single RNA that literally regulates six different biological processes,” Jones says.

lncRNAs can play different roles in a cell thanks to their ability to readily change conformations, a process that alters what molecules they can bind to. To better understand the biochemistry of lncRNAs, scientists need to better characterize all these structures. But determining the structure of a lncRNA is no easy task. “We know a lot about protein structures, but we know relatively little about RNA structure,” says Michael Summers, a biochemist at the University of Maryland, Baltimore County, and one of Jones’s colleagues in the field.

While the inherent flexibility of RNA enables it to take on many shapes, and subsequently functions, that flexibility also makes it challenging to crystallize and study with X-ray crystallography or cryo-electron microscopy, the standard approaches to studying protein structure. Many researchers use nuclear magnetic resonance spectroscopy to determine RNA structure. Unfortunately, Jones says, NMR is more effective for short strands of RNA, not lncRNAs. So Jones chops them up.

She and her team deploy a combination of molecular biology techniques that allow them to clip a lncRNA into structured regions that fold independently of the parent strand. Then the scientists can use NMR to determine the 3D structures of those smaller pieces. The lab’s computational modeling programs can join those smaller 3D structures into a larger structure of the lncRNA, allowing the scientists to start to understand how the RNAs move through different conformations.

Some of those lncRNA conformations are associated with disease states. “The ultimate goal is to identify a structured state that we can block with some sort of therapeutic agent,” Jones says.

As Jones pursues this goal, she also works to provide high school students from economically disadvantaged or other underrepresented groups with hands-on research opportunities in her laboratory. Despite an early interest in science, Jones says, she didn’t have anyone teaching her what it meant to be a scientist until high school, when she started working in a structural biology lab at the University of Toledo.

Now she has designed her own program to teach high schoolers lab skills. Last year, Jones published a preprint of their work—one that hasn’t gone through peer review—on determining how a specific RNA-binding protein interacts with lncRNAs. “I had three students who worked on a project with me last summer,” she says, “and they’re right in the author list with the PhD students.”

Jones’s aptitude for teaching was evident to her postdoctoral adviser, Michael Sattler, a biochemist at the Technical University of Munich. He recalls Jones as both a passionate scientist and an effective teacher. After Jones completed her postdoc, Sattler wasn’t sure the other students would be able to independently run the experiments Jones had worked on. But it was needless to worry. He was impressed by the skills she’d passed on to them. Ultimately, he suspects that Jones is bound to be an enthusiastic and skilled leader in her field.

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