Nediljko (Ned) Budisa, a U of M chemistry professor, is investigating ways to expand the genetic code to create proteins with new chemical properties (properties not found), with potential applications in medicine, biotechnology and wound healing.
“Fundamentally, the genetic code is one of the deepest organizing principles shared by life on Earth,” Budisa said. It is a system through which information stored in genes is translated into proteins. These proteins perform essential functions in living organisms, from maintaining tissue structures to supporting biological processes.
Most proteins are made from 20 standard amino acids which serve as their basic building blocks. However, these amino acids have chemical limitations. Proteins can become damaged, lose their structure or stop functioning under certain conditions.
Budisa, the Tier 1 Canada Research Chair in Chemical Synthetic Biology focuses on introducing additional amino acids into proteins to improve their chemical properties. His team works in genetic code engineering, chemical synthetic biology and xenobiology, a field that develops biological systems with chemical components different from those found in nature.
“Conventional genetic engineering changes the message written in DNA; we ask whether we can also change some of the rules by which that message is translated into chemistry,” Budisa explained.
By engineering the cellular systems responsible for producing proteins, researchers can introduce non-standard amino acids at specific positions. These additions could make proteins more resistant to oxidation — a chemical process in which electrons are lost during chemical reactions — improve their stability or introduce new chemical functions.
However, Budisa emphasized that incorporating unusual amino acids does not necessarily mean scientists have rewritten the genetic code. Current methods largely rely on modifying how existing cellular machinery operates. Developing a “genuinely altered coding system” that remains efficient and stable over time presents further challenges.
One of Budisa’s current projects investigates enzymes found in organisms adapted to extreme cold. These enzymes, known as aminoacyl-tRNA synthetases, help cells translate genetic information into proteins. According to Budisa, their natural flexibility makes them useful candidates for introducing new amino acids into proteins.
His team recently demonstrated that cold-adapted systems can function efficiently as specialized machinery for protein production. An area open for further investigation is whether these systems can support more reliable methods of producing designer proteins.
Budisa is also interested in neurodegenerative diseases and age-related conditions, where proteins may become damaged, lose their structure or accumulate in harmful ways.
Developing proteins with greater resistance to damage could eventually support new therapeutic approaches. According to Budisa, one possibility involves temporarily changing the proteins produced by cells without permanently modifying their DNA. A system based on messenger RNA, or mRNA, could instruct cells to produce a modified protein for a limited period before the RNA naturally breaks down.
Budisa said this approach could offer different possibilities for controlling treatments compared to permanent gene editing.
His research also extends to wound healing. Working with colleagues across synthetic biology, engineering, immunology and medicine, Budisa is exploring materials that could actively support the healing process. These include engineered synthetic skin, therapeutic adhesive powders and materials designed to respond to changes in wounds.
The long-term goal is to develop treatments that do more than cover injuries by helping manage infection, inflammation and tissue regeneration. However, Budisa stressed that these applications remain under development.
“Demonstrating that something is possible is the beginning of technology development, not its end,” he said.
For Budisa, researchers must establish whether engineered proteins can be produced consistently, function in biological systems and eventually meet the requirements for medical use.
Beyond technological applications, Budisa’s work asks questions about how biological systems evolved. He has spent more than 30 years investigating why living organisms use their existing genetic code and whether alternative systems could function. For future research, he hopes to explore whether changes to the genetic code can become stable features of living cells rather than temporary laboratory modifications.
Budisa also showed concern about the ethics surrounding research and technology development in the field. “Do we, as scientists, think seriously enough about the consequences of the experiments we perform and the technologies we create?”
He agreed researchers must consider who benefits from these developments and what responsibilities accompany scientific advances.
For students interested in research, Budisa encouraged curiosity and a willingness to investigate unsuccessful experiments.
“Negative results can sometimes tell you considerably more than spectacular positive results,” he said.
