From left: DCU scientists Natasha McStay and Zara Molphy. Image: DCU
DCU scientists Natasha McStay and Dr Zara Molphy have discovered how opiates can collapse DNA, with possible implications for gene delivery. Claire O’Connell reports.
Opiate drugs such as morphine are well known for their pain-relieving properties. But could these poppy-derived chemicals also be useful for binding and ‘compacting’ DNA when we want to deliver genes into cells?
That’s an intriguing possibility raised by the work of scientists at Dublin City University (DCU), who have found that opiate compounds can bind to DNA and condense it.
Surprising binding
“We were surprised by the results,” said Natasha McStay, joint-first author on the study published earlier this year in the journal Nucleic Acids Research. “It had not been shown in the scientific literature that opiates bind DNA.”
McStay is in the third year of her PhD in the lab of Dr Andrew Kellett, who led the study at DCU School of Chemical Sciences. She made the discovery when she screened various opiate chemicals for their ability to bind to DNA. “I generated a large library of opiates and we discovered a hit compound binding to DNA,” she explained.
To take a closer look at what was happening, McStay and colleague Dr Zara Molphy made variations of the morphine compounds in the lab and ran a series of tests to measure results. They saw that when specific opiate compounds bound to the surface of DNA, the double helical structure condensed or collapsed.
Well done Natasha McStay and @ZMolphy! First ever observation of opiate-nucleic acid binding interactions @DCU_Research @EU_H2020 @nicb_dcu https://t.co/cnqVUIVcMH
— Andrew Kellett (@andrew_kellett) December 6, 2016
Collapsing DNA
The discovery has generated a lot of interest, according to Molphy, because being able to collapse the structure of DNA may be useful if you want to ‘transfect’ or move DNA artificially into a cell.
“Researchers use viral vectors to transfect or carry foreign DNA into a cell, but there can be side effects,” she said. “Being able to aggregate DNA like this means you may be able to transport DNA in this condensed state without damaging it and avoid the need to use viral vectors.”
The two scientists are now using a technique called ‘click chemistry’ to build a larger library of opiate compounds with potential DNA-binding abilities.
They are also continuing to research how small changes in the environment of the cell, such as pH or salt concentration, could affect the condensation properties of the opioids bound to DNA. Knowing this would aid the design of an opiate-based DNA transfection system that prepares DNA for delivery into the cell and releases it once inside.
Natasha McStay with PhD supervisor Dr Andrew Kellett. Image: DCU
Combining disciplines
McStay won the Colin Barnes prize for outstanding postgraduate research at DCU Chemistry Day last month and she will present at the 69th Irish Universities Chemistry Research Colloquium later in June.
She studied biology and chemistry for Leaving Cert before her degree in chemical and pharmaceutical sciences at DCU, and she credits her grandparents with igniting her interest in asking questions about science.
Molphy has followed a similar path, studying for the same undergraduate degree and completing her PhD in Kellett’s lab before starting a Science Foundation Ireland-funded postdoctoral fellowship in February.
Both researchers love how their work allows them to explore both chemistry and biology. “Our group in DCU has a lot of different types of expertise and we are lucky as that lets us work on projects that involve mixed disciplines,” said Molphy.
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