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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
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Headshot of Sarah Lovelock Headshot of Sarah Lovelock
Credit: Courtesy of Sarah Lovelock
May 17, 2024 | A version of this story appeared in Volume 102, Issue 15
Synthesis
“Developing
new approaches
to oligonucleotide
manufacturing”
Sarah  Lovelock

Sarah Lovelock isn’t the type of person to engage in much fuss or fanfare surrounding her work—she prefers to just get down to business tackling knotty science problems. So it’s fitting that the problem she’s working on is developing low-fuss ways to make oligonucleotide drugs using enzymes.

Vitals

Current affiliation: University of Manchester

Age: 36

PhD alma mater: University of Manchester

Hometown: Watford, England

My role model is: “Carolyn Bertozzi, not only for her scientific achievements at the chemistry and biology interface but for her contributions to promoting equality and diversity in science. I enjoy working with a diverse and multidisciplinary research team and hope that I too can contribute to creating an inclusive scientific community.”

My lab superpower is: “I can pipette with both hands!”

Therapeutic oligonucleotides are short strings of nucleic acids, about 20 bases long, designed to bind to messenger RNA and prevent it from making harmful proteins. They’re a promising class of treatments for a variety of diseases, including muscular dystrophy and cancer. But as the number of oligos in the drug development pipeline grows, so does the need for scalable ways to produce them.

One thing that’s preventing oligonucleotides from reaching their full potential is manufacturing. They’re hard to make efficiently on a large scale, says Lovelock, who researches oligonucleotide synthesis at the University of Manchester. The traditional way to make oligos involves a four-stage process to add each base to a chain, which is inefficient and generates considerable waste.

Lovelock avoids this lengthy process by using two enzymes to assemble oligonucleotide chains, a tactic inspired by how these chains are made in living organisms. First, a DNA polymerase forms the oligo by adding nucleoside triphosphate building blocks to a template strand of DNA. Then an endonuclease snips off the finished chain, regenerating the template so that it can be used over and over to make many copies of the oligonucleotide product—all in one pot.

Lovelock says she had always felt drawn to the science of making molecules to improve people’s lives and health. She became interested in using enzymes for synthesis during an internship year at Roche in 2008 while she was doing her undergraduate degree at the University of Leeds. “We had some challenging chemistry that wasn’t working. So I went over to the biocatalysis group and screened some enzymes. And they worked. That was the first time I really saw the power of enzymes,” she says.

Lovelock went on to do PhD research in Nicholas Turner’s lab at the University of Manchester, exploring enzymes to make chiral amines. She was “a very easy student to supervise,” Turner says—organized, hardworking, and self-assured.

Those qualities impressed potential employers as well, Turner adds. At the end of her PhD, in 2014, GlaxoSmithKline “realized she was a bit of a star” and wooed her to work for the firm, Turner says. Lovelock spent 4 years at the company, engineering enzymes to make pharmaceuticals. It’s there that she first became acquainted with oligonucleotide drugs.

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And then in 2017, she did something unusual: she returned to academia as a postdoctoral scholar in Anthony Green’s lab at the University of Manchester.

“Working in industry was a valuable experience because I saw what it takes to get a molecule through to market,” she says. But Lovelock wanted to tackle more high-risk, long-term research questions that she realized were better suited to an academic laboratory.

In 2020, Lovelock received a Future Leaders Fellowship from UK Research and Innovation, the country’s main research funding agency, and a grant from the university so she could start her own lab and pursue her ambitious ideas in the realm of oligonucleotide synthesis. Her lab’s first publication was a 2023 paper in Science detailing the dual-enzyme system the team had developed.

Turner says that it’s been “good fun” to see Lovelock grow in her career, from a graduate student to a departmental colleague who contributes a great deal of intellectual firepower and unique insight from her time working in industry. For example, she introduced automated enzyme engineering tools that have benefited the entire institute where she and Turner work. “The key is for us to keep her,” he says.

Lovelock is very modest about her rising-star status, which she credits in large part to teamwork within the scientific community and the opportunity to build on previous advances. She says that being able to work across disciplinary lines to solve big problems is what makes her job interesting. “I think it really is going to be a team effort” to realize the potential of enzymes and oligonucleotides for medicine, she says.

Biocatalysis

Sarah Lovelock

This biological chemist streamlines oligonucleotide synthesis

by Brianna Barbu
May 17, 2024 | A version of this story appeared in Volume 102, Issue 15
Sarah Lovelock.

Credit: Courtesy of Sarah Lovelock/C&EN | Sarah Lovelock

 

Vitals

Current affiliation: University of Manchester

Age: 36

PhD alma mater: University of Manchester

Hometown: Watford, England

My role model is: “Carolyn Bertozzi, not only for her scientific achievements at the chemistry and biology interface but for her contributions to promoting equality and diversity in science. I enjoy working with a diverse and multidisciplinary research team and hope that I too can contribute to creating an inclusive scientific community.”

My lab superpower is: “I can pipette with both hands!”

Sarah Lovelock isn’t the type of person to engage in much fuss or fanfare surrounding her work—she prefers to just get down to business tackling knotty science problems. So it’s fitting that the problem she’s working on is developing low-fuss ways to make oligonucleotide drugs using enzymes.

Therapeutic oligonucleotides are short strings of nucleic acids, about 20 bases long, designed to bind to messenger RNA and prevent it from making harmful proteins. They’re a promising class of treatments for a variety of diseases, including muscular dystrophy and cancer. But as the number of oligos in the drug development pipeline grows, so does the need for scalable ways to produce them.

One thing that’s preventing oligonucleotides from reaching their full potential is manufacturing. They’re hard to make efficiently on a large scale, says Lovelock, who researches oligonucleotide synthesis at the University of Manchester. The traditional way to make oligos involves a four-stage process to add each base to a chain, which is inefficient and generates considerable waste.

Lovelock avoids this lengthy process by using two enzymes to assemble oligonucleotide chains, a tactic inspired by how these chains are made in living organisms. First, a DNA polymerase forms the oligo by adding nucleoside triphosphate building blocks to a template strand of DNA. Then an endonuclease snips off the finished chain, regenerating the template so that it can be used over and over to make many copies of the oligonucleotide product—all in one pot.

Lovelock says she had always felt drawn to the science of making molecules to improve people’s lives and health. She became interested in using enzymes for synthesis during an internship year at Roche in 2008 while she was doing her undergraduate degree at the University of Leeds. “We had some challenging chemistry that wasn’t working. So I went over to the biocatalysis group and screened some enzymes. And they worked. That was the first time I really saw the power of enzymes,” she says.

Lovelock went on to do PhD research in Nicholas Turner’s lab at the University of Manchester, exploring enzymes to make chiral amines. She was “a very easy student to supervise,” Turner says—organized, hardworking, and self-assured.

Those qualities impressed potential employers as well, Turner adds. At the end of her PhD, in 2014, GlaxoSmithKline “realized she was a bit of a star” and wooed her to work for the firm, Turner says. Lovelock spent 4 years at the company, engineering enzymes to make pharmaceuticals. It’s there that she first became acquainted with oligonucleotide drugs.

And then in 2017, she did something unusual: she returned to academia as a postdoctoral scholar in Anthony Green’s lab at the University of Manchester.

“Working in industry was a valuable experience because I saw what it takes to get a molecule through to market,” she says. But Lovelock wanted to tackle more high-risk, long-term research questions that she realized were better suited to an academic laboratory.

In 2020, Lovelock received a Future Leaders Fellowship from UK Research and Innovation, the country’s main research funding agency, and a grant from the university so she could start her own lab and pursue her ambitious ideas in the realm of oligonucleotide synthesis. Her lab’s first publication was a 2023 paper in Science detailing the dual-enzyme system the team had developed.

Turner says that it’s been “good fun” to see Lovelock grow in her career, from a graduate student to a departmental colleague who contributes a great deal of intellectual firepower and unique insight from her time working in industry. For example, she introduced automated enzyme engineering tools that have benefited the entire institute where she and Turner work. “The key is for us to keep her,” he says.

Lovelock is very modest about her rising-star status, which she credits in large part to teamwork within the scientific community and the opportunity to build on previous advances. She says that being able to work across disciplinary lines to solve big problems is what makes her job interesting. “I think it really is going to be a team effort” to realize the potential of enzymes and oligonucleotides for medicine, she says.

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