Scientists Develop Process Using Molecules in the Cell to Identify Environmental Signals
An effort involving Rutgers researchers could have applications for disease detection and environmental monitoring
Scientists have transformed RNA, a biological molecule present in all living cells, into a biosensor that can detect tiny chemicals relevant to human health.
Research by Rutgers University-New Brunswick scientists centers on RNA, a nucleic acid that plays a crucial role in most cellular processes. Their work is expected to have applications in the surveillance of environmental chemicals and, ultimately, the diagnosis of critical diseases including neurological and cardiovascular diseases and cancer.
“Imagine that people will go to the hospital and give a sample of cells from their own bodies for regular check-ups,” said Enver Cagri Izgu, an assistant professor in the Department of Chemistry and Chemical Biology in the Rutgers School of Arts and Sciences and the corresponding author of the study. “And there will be some technology involved in transforming their cells into sensor cells without changing their frame and physiology. Those cells would then be returned to the person’s body, and the body will never have the issue of rejecting because it's their own cells. Those cells will have the ability to talk to us and generate signals about whether we have traces of toxic chemicals or the beginnings of disease within us.”
In the journal Angewandte Chemie International Edition, Izgu and his team reported how they implemented RNA within bacterial cells in such a way that these cells, and even their daughter cells, were able to detect distinct chemicals. Such substances to be detected can be short-lived inorganic chemicals central to many physiological processes, both in healthy and disease states. RNA normally would not interact with these types of chemicals, and it would be exceedingly challenging to sense them through complex genetic circuits.
Scientists are actively investigating aspects of RNA to understand its multiple functions and its potential for improving human health. One unusual RNA function, first disclosed in 2011, is the ability of RNA to bind small molecules to generate light. This seminal study inspired Izgu and his team to push the boundaries of the RNA-induced light generation concept.
“We used our chemistry knowledge and turned RNA into a detector for physiologically important and short-lived inorganic chemicals, such as hydrogen sulfide and hydrogen peroxide,” Izgu said. “The inorganic chemical we want to detect first reacts with a small receptor molecule, which in turn becomes a binder of a special RNA sequence. The subsequent binding event between the receptor product -- a hydroxybenzylidene imidazolinone derivative -- and the RNA generates light at a specific wavelength. We achieved this chemical sensing mechanism inside living Escherichia coli as the model organism.”
The work is novel because although an externally designed RNA can be produced within cells, it can’t be coaxed to detect hydrogen sulfide or hydrogen peroxide.
In the critical stages of cancer and neurological and cardiovascular diseases, the human cells produce different levels of hydrogen sulfide and hydrogen peroxide. Izgu and his team were able to detect these chemicals using their E. coli sensors under laboratory conditions.
Izgu said the ultimate goal of the Rutgers research is to transform a human cell into a sensor cell in a similar way they were able to make the E. coli sense traces of chemicals.
Izgu and co-author Tushar Aggarwal, a former doctoral student in the Department of Chemistry and Chemical Biology, are co-inventors in a patent application filed by Rutgers University on this work.
Other Rutgers scientists who contributed to the study included: Liming Wang and Sarah Cho (both current), and Bryan Gutierrez (former), doctoral students in the Department of Chemistry and Chemical Biology; Huseyin Erguven, a former postdoctoral associate who is now working at Paraza Pharma Inc. in Montreal; and Hakan Guven, a student at Robert Wood Johnson Medical School.
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