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Center college biochemist
From a younger age, Sikes appeared on the world with an insatiable curiosity about how issues labored. She collected and noticed all the pieces from rocks to snakes. “I drove my elementary college lecturers loopy,” she says.
In center college, she was already designing experiments to measure the chemical reactions in nature, together with a toxicology research of caffeine’s results on sea urchins. She’d hoped to influence her father—a scientist himself—to reasonable his espresso behavior. Whereas the experiment was unsuccessful in that regard, it planted a seed for one thing higher. Sikes was realizing how chemistry analysis may promote good well being and profit society.
Though her undergraduate research at Tulane targeted on bodily chemistry, Sikes finally circled again to her early biochemical analysis. At Stanford, the place she earned her PhD, she started finding out redox mechanisms, significantly how sure oxidizing brokers pull electrons from different molecules. And she or he turned desirous about oxidative stress, which happens when free radicals within the physique—extremely reactive molecules lacking a number of electrons that readily oxidize different substances—overwhelm the antioxidants that cells usually produce to neutralize them. This could trigger quite a lot of well being issues.
Specifically, most cancers is characterised by higher-than-usual ranges of free radicals referred to as reactive oxygen species (ROS). In regular metabolic exercise, ROS molecules promote cell regeneration and gene expression. However elevated ROS manufacturing can hurt regular cells and facilitate tumor development.
As a biochemist, Sikes was fascinated by the prospect of sensing and manipulating these modifications, which docs have struggled to measure precisely in most cancers cells. To see what was taking place inside tumors, she wanted to see when cells had been oxidized; she turned to fluorescent proteins that emit mild at completely different wavelengths. “To detect these redox reactions, we use chemistry that’s triggered by mild,” says Sikes.
It was solely a brief step to translate that into therapeutic potential. If docs can perceive the precise redox exercise underlying a tumor, they’ll higher predict how chemotherapy will arrest that exercise—and permit regular cells to regain management.
In any other case, they’ll proceed taking pictures at nighttime. Sikes had a imaginative and prescient of illuminating their quest—actually.
Sensors at work
Utilizing her sensors, researchers may probably measure when, the place, and the way a lot the tumors are experiencing oxidation—just by lighting them up. The fluorescent sensors may additionally make clear numerous therapeutics’ mechanism of motion, thereby serving to docs choose one of the best ones for every affected person.
Since 2018, Sikes’s group has been collaborating with Tufts pathologist Arthur Tischler to make use of their biosensors for perception into the redox chemistry behind numerous cancers. In a paper revealed in 2020, they explored the pathology of tumors poor in succinate dehydrogenase (SDH), an important metabolic enzyme and an inhibitor of ROS manufacturing. Low ranges of SDH have been linked to cancers which are each uncommon and tough to deal with.
By reengineering biochemical processes, she will be able to measure the distinctive chemistry behind antibody manufacturing, tumor growth, and nearly all features of human illness.
Utilizing the identical biosensors, Sikes and her group turned the primary to concentrate on chemotherapies that induce a single oxidizing agent: hydrogen peroxide. In a paper revealed in Cell Chemical Biology, they define how they created a sensor particularly designed to detect elevated hydrogen peroxide concentrations, which may selectively kill most cancers cells. The group examined 600 molecules as potential therapeutics, figuring out 4 that boosted hydrogen peroxide within the tumor samples.
The group’s achievement will facilitate scientific trials of latest prescription drugs. The subsequent step, ideally, is to make use of these fluorescent sensors to judge the results of these therapeutics in patient-derived tumors.
Fast-detection diagnostics
Sikes realized that her method may additionally detect pathogens—together with SARS-CoV-2, the novel coronavirus that causes covid-19.
To make such a detector, Sikes wanted antibody proteins that might react with the distinctive proteins of the virus. However these reactive proteins didn’t exist. So she determined to create them.
In her postdoc analysis, Sikes had labored with Caltech chemical engineer and 2018 Nobel laureate Frances Arnold, a pioneer in creating novel proteins with fascinating properties.
Sikes’s lab now engineers proteins that lock onto the distinctive folds within the proteins attribute of assorted pathogens. The engineered proteins emit completely different wavelengths relying on how they bond with the virus’s or bacterium’s materials.
On the idea of this progressive expertise, Sikes has developed speedy diagnostic exams incorporating a set of reagents that discover one species and exclude the others, so well being professionals can extra rapidly and precisely diagnose infectious ailments. Her lab focuses on engineering reagents that may determine coronaviruses, respiratory syncytial virus (RSV), and different causes of respiratory illness; micro organism that have an effect on meals security (significantly Listeria and E. coli); and parasitic eukaryotes resembling Plasmodium, which causes malaria.
COURTESY OF THE RESEARCHERS
Sikes’s college students and postdocs at her Singapore lab are actually creating exams that assess immunity in opposition to completely different covid-19 variants as a part of a fast-tracked analysis challenge. As in her different research, specifically engineered proteins will react uniquely with every particular person’s repertoire of antibodies—permitting the group to higher perceive the extent and sturdiness of immunity to covid on a person stage.
Sikes’s effort to avoid wasting lives with rising biosensor expertise is simply a part of her mission to make use of chemistry analysis for society’s profit. She accepted her place at MIT in 2009 largely due to its fame for analysis that might be utilized to resolve social issues. And to advance that mission nonetheless additional, she cherishes her alternatives to mentor aspiring scientists.
Each summer season, MIT accepts budding researchers from traditionally underrepresented areas and faculties. Final summer season, Sikes mentored college students from Spelman School, Morehouse School, and the College of Puerto Rico–Mayagüez. This system gives hands-on alternatives to do analysis and construct connections with the Institute’s community of scientists. As a part of an MIT alternate program, Sikes additionally mentors undergraduates at Imperial School London.
To Sikes, that is the epitome of what science schooling must be. “I be taught in all probability as a lot from them as they be taught from me,” she says. “I actually view it as a collaboration. I’ve been doing this for 20 years now … however all these college students and postdocs include their very own backgrounds and experiences and methods of taking a look at issues. Typically, they’ve concepts or hypotheses that wouldn’t have occurred to me.”
Redox to the rescue
The mysteries that Sikes has been chasing since childhood have all come all the way down to measurement: What invisible reactions drive floor phenomena?
Immediately, by reengineering biochemical processes, she will be able to measure the distinctive chemistry behind antibody manufacturing, tumor growth, and nearly all features of human illness. Within the subsequent few years, she hopes to finalize the biosensor proteins and get them to market, empowering different researchers to enhance affected person outcomes and mitigate the following pandemic.
That’s to not say Sikes’s lifelong curiosity has been sated. There are at all times additional inquiries to be requested. “I hope 10 years from now we’ll be doing one thing completely completely different that I can’t even think about proper now,” she says.
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