JAKARTA – Manufacturing nanocomputers used for precision healthcare has long been the dream of many scientists and healthcare providers. Now, for the first time, researchers at Penn State have produced a nanocomputer that can control the function of certain proteins involved in cell movement and cancer metastasis. This research paved the way for the construction of complex nanocomputers for the prevention and treatment of cancer and other diseases.
Nikolay Dokholyan, Professor G. Thomas Passananti, Penn State College of Medicine, and his colleagues—including Yashavantha Vishweshwaraiah, postdoctoral scholar in pharmacology, Penn State—invented transistor-like ‘logic gates’, which are a type of computational operation in which multiple inputs control the output.
“Our logic gate is only the beginning of what you might call mobile computing, but it is a major milestone because it demonstrates the ability to embed conditional operations in proteins and control their function,” said Dokholyan. “This allows us to gain a deeper understanding of human biology and disease and introduces possibilities for the development of precision therapies.”
The team’s logic gate consists of two sensor domains designed to respond to two inputs—light and the drug rapamycin. The team targeted the protein focal adhesion kinase (FAK) because it is involved in cell adhesion and movement, which is an early step in the development of metastatic cancer.
“First, we introduced a rapamycin-sensitive domain, called uniRapr, which had previously been designed and studied by the lab, into the gene encoding FAK,” said Vishweshwaraiah. “Next, we introduced a light-sensitive domain, LOV2. After we optimized the two domains, we combined them into one final logic gate design.”
The team inserted the modified gene into HeLa cancer cells and, using a confocal microscope, observed the cells in vitro. They studied the effects of each input separately, as well as the combined effect of the inputs, on cell behavior.
They found that not only were they able to rapidly activate FAK using light and rapamycin, but also that this activation resulted in cells undergoing internal changes that increased their adhesive ability, ultimately decreasing their motility.
Their findings were published Tuesday (November 16) in the journal Nature Communications. “We show for the first time that we can build a functioning nanocomputing agent inside a living cell that can control cell behavior,” said Vishweshwaraiah. “We also discovered some interesting features of the FAK protein, such as the changes it triggers in cells when activated.”
Dokholyan notes that the team hopes to eventually test these nanocomputing agents in vivo in living organisms. (E-4)
News Source: RRI.
–
