Enzyme Time: Stevens Summer Scholar produces key enzyme for medical researchers


In the 'pyramid' of new drug development, assessment of proteins and enzymes occupy the all-important 'base': without effective compounds that bind to target proteins or enzymes, new therapies cannot be effectively tested for their abilities to disrupt disease pathways.

And one Stevens Summer Scholar has been working to produce and purify those all-important supporting players on the drug development team.

Matteo Sturla '15, a junior from Hillsborough, New Jersey majoring in biomedical engineering and a striker on the varsity men's soccer team, split his summer between Stevens and Memorial Sloan-Kettering Cancer Center in New York City. While his work at Sloan-Kettering is strictly engineering-based — he's working on a new IV-drip detector — his Stevens project helped support a new Stevens team focused on the development of the drugs and therapies of the future. Through the Office of Innovation & Entrepreneurship's Summer Scholar program, he's working to help purify and produce a supply of BirA, a type of biotin ligase…and a star enzyme in medical circles.

"Biotin ligase is a very useful enzyme for medical research, because it enables many biochemical assays in drug discovery," explains Sturla's adviser, Dr. Naoko Tanaka, a pharmaceutical researcher and visiting research associate in Stevens' Center for Healthcare Innovation (CHI).

Sturla hails from a medical family: his grandfather enjoyed a long career as a cardiologist, while his father continues practicing as a veterinarian. Sturla himself plans to enter medical school within a year or two of graduating Stevens, with aspirations of becoming a physician.

"That's my life's passion and aspiration," he smiles. "I want to follow in my dad's and grandfather's footsteps as a medical doctor."

To purify the biotin ligase BirA, he repeats a complex sequence of steps over several days. First Sturla implants a plasmid DNA that encodes information of a protein of interest into cells of E.coli bacteria, then grows the bacterial cells at various temperatures until proteins are optimally expressed. Then he purifies the resulting proteins using a technique known as affinity chromatography, in which an 'affinity tag' of peptides binds to the specific resin. Sturla has successfully developed a novel purification method, and the results, so far, have been excellent: BirA with high purity.

"This biotin ligase he is producing is higher-quality than that which is commercially available," explains Tanaka. "This is important. We also hope that it also proves to be more 'active,' as well."

Should it prove highly active, Sturla's BirA will then be used as building blocks for drug discovery work by Tanaka and her Stevens research group. The enzyme will be particularly helpful when investigating the interactions of proteins that may cause diseases in combination.

Researchers seeking clues to those mechanisms must that multi-protein interaction somehow — and one of the best ways to do it is to disrupt the interaction. Biotin ligase has a strong affinity for a specific protein known as streptavidin, and this strong propensity to bind to each other can be used to immobilize a 'target' disease protein and measure its actions.

"The beauty of this enzyme is its universal use," concludes Tanaka. "It can be used to study almost any type of protein. That makes it especially useful for our purposes."