Colorado’s universities lead bioscience charge

BOULDER — The exterior looks like a factory, and the interior is cavernous. The Jennie Smoly Caruthers Biotechnology Building dominates the university’s East Campus.

But the building is not simply an impressive addition to the Boulder skyline. The University of Colorado Boulder’s 336,800-square-foot, $145 million research facility is the new home of the university’s chemical and biological engineering program and hosts some of the groundbreaking bioscience research that is being conducted around the state.

Gillespie Professor of Bioengineering Ted Randolph said the building satisfies the needs of his laboratory, which evolved along with the field of chemical engineering.

His previous lab in CU’s engineering center was set up with petrochemical engineering in mind, Randolph said. The Jennie Smoly Caruthers Biotechnology Building gives him a new lab orientation with more adequate machinery and places him closer to other researchers in his field.

Randolph’s work focuses on development of protein-based pharmaceuticals, which are the fastest-growing class of new drugs. More than half of new drugs are protein-based, he said.

Among the prominent protein-based pharmaceuticals are Human Growth Hormone and the breast cancer drug Herceptin. Drugs for rheumatoid arthritis are all protein-based, and brought in around $16 billion in profit last year, Randolph said.

One of the challenges of Randolph’s research is ensuring that protein-based pharmaceuticals are both chemically and conformationally pure. The molecules not only need to be of the same chemical composition, but the proteins also need to be folded properly, he said.

“Proper structure and folding determine if it (protein-based pharmaceutical) works,” Randolph said. “Unfolding a protein is like scrambling an egg.”

Randolph isn’t the only researcher conducting important vaccine work at Colorado’s universities.
Potential breast cancer treatment

Thirty-one miles to the south, at the University of Colorado Anschutz Medical Campus, SixOne Solutions is in the beginning phases of testing new cancer treatments.

Founded by Associate Professor of Pharmacology Heide Ford and Associate Professor of Biochemistry Rui Zhao, SixOne Solutions is developing drugs to counteract  the cancer-related Six1 and Eya2 proteins, SixOne CEO Ginny Orndorff said.

The Six1 protein is involved in embryo production and is normally “turned off” before birth, but it is sometimes turned back on in cancer and causes tumors to grow, Orndorff said.

Fifty percent of breast-cancer tumors and more than 90 percent of metastasized tumors analyzed had Six1, Orndorff said, adding that Six1 is both a cause and catalyst of cancer.

In July 2013, SixOne received the BioScience Discovery Evaluation Grant to test drug-like compounds on mice. The compounds are designed to treat the aggressive, “triple negative” form of breast cancer that doesn’t respond to hormonal treatment or the common breast cancer drug Herceptin, Orndorff said.

SixOne is testing cell cultures to narrow the number of compounds down from the thousands to one or two before they begin animal testing, Orndorff said.

It will be some time before the compounds are ready for human testing. Orndorff expects animal testing to begin “in the next month or two,” with human testing at least five years away.

“It’s a very structured process to get the FDA to think it’s safe enough before you put it in even one person,” she said.

Still, the potential to develop a universal cancer treatment is enormous. Six1 is also found in ovarian, lung, and brain cancer cells.

“If it (Six1) is no longer functional in cancer cells, then they no longer function as cancer cells,” Orndorff said.
Orndorff credited Colorado for fostering a research-friendly environment.

“It’s a critical mass of great research,” she said.

Studying crabs to save an industry

Colorado’s bioscience research isn’t limited to medical fields.

At Colorado State University’s Crab Lab, Professor Don Mykles studies molting in land crabs. The lab studies the role of the negative muscle regulator myostatin in molting.

Mykles said myostatin plays a different role in crustaceans during molting than it does in mammals.

Land crabs must reduce their muscle mass during molting to shed their shells, which Mykles said he expected to correspond with an increase in myostatin.

Instead, land crabs see an increase in protein synthesis during molting. That accompanies a compensatory increase in protein degradation, which allows for a rapid turnover of protein to help the crab molt, Mykles said.
Mykles also received a $1 million grant from the National Science Foundation in March 2013 to study how the nervous system affects the molting glands.

The project will examine changes in gene expression in response to external triggers, Mykles said.

To do that, the lab will create a transcript library by cataloging every gene in the molting cycle. The initial reads suggest a catalog of 40 to 50 thousand genes, Mykles said.

The Crab Lab will have a preliminary transcript by the end of the year. Not all the genes they catalog are involved in molting regulation, so the lab will focus on the several hundred most important ones in the next step of the project as it quantifies changes in genes during the molting cycle, Mykles said.

A major focus of the project is the impact changes in climate and acidification have on the molting gland.
Economically important species, such as New England lobster, could be threatened by climate change. The gene catalog will be available to fisheries to help them better understand molting and lessen the detrimental effects of pollution and climate change, Mykles said.

on Facebook on LinkedIn