Undergraduate researcher targets drug-resistant bacteria

Drug-resistant bacteria are a growing threat to the health of the world. Larsen Birdsong hasn’t even graduated yet, but he’s helping tackle the problem.

Birdsong, who is majoring in chemistry and biochemistry, is an undergraduate researcher in associate professor of chemistry Alan Schwabacher’s lab. He’s focused on synthesizing a chemical compound that will target aspects of drug-resistant bacteria to knock out their defenses and make them treatable by antibiotics.

He presented his research at the virtual UWM undergraduate research symposium in April. It was a great experience to culminate his literal years of research experience at the university.

“At a big school like Madison, you can’t really do undergraduate research. Here, it was a lot better. That’s specifically why I chose UW-Milwaukee,” Birdsong said.

He began his work the summer before his freshmen year by participating in UWM’s UR@UWM summer research program, which allows incoming first-years to spend their summer working with UWM professors on various research projects.

Birdsong kept at it when he became a full-fledged student.

“I got involved in my current research when I was going through a list of available research projects, and Dr. Schwabacher’s research really interested me. I emailed him, we had a meeting, and now I work in his lab!”

Currently, Birdsong is focusing on drug-resistant, or gram negative, bacteria.

“Gram negative bacteria are resistant to drugs because they have an outer membrane made up of many proteins, and particularly a ‘beta-barrel.’ It’s like a beta sheet wrapped (around) the bacteria,” he explained. “Those beta barrels are made by what we call the BAM – the beta-barrel assembly machine.”

Other researchers have already found a strand of RNA, which codes the genetic material for proteins, that disrupts the BAM. Unfortunately, RNA does not a good drug make; the human body breaks down the foreign RNA before it can work against drug-resistant bacteria.

So, those researchers made a compound that mimics the function of that particular RNA. It inhibits the BAM.

“When that’s inhibited, the proteins on the outside (of the gram-negative bacteria) won’t be composed correctly and will allow other antibiotics to get into the cell and kill it,” Larsen said. “That’s, of course, important, because bacteria, as evolution goes, are getting more and more resistant to drugs.”

The problem is, that compound is expensive, difficult to make, and yields very little effective material.

Birdsong’s job is to synthesize an analog compound that will be easier and more efficient to make. It can be slow going, but that’s how research works, he said.

“I’ll run a reaction, work it up, and see if it worked. If it didn’t work, I’ll try something new,” he added. “There’s no textbook you can go to to make sure what you’re doing will work. You just have to wait and see. That’s science. You’ve got your hypothesis, and then you’ve got all of your testing to test it out.”

He and other members of Schwabacher’s lab are still working toward their goal, but Birdsong says his early results do show some promise – “in my undergraduate opinion,” he hastened to add. “I think that a lot of the things I’ve been doing have worked well and shown that it’s possible.”

And in the meantime, his research has taught him a lot, and not just about bacteria.

“I’ve learned about how chemical synthesis works, which is really interesting. I’ve learned a lot of good lab techniques,” Birdsong said. “I’m really lucky to have the experience at Milwaukee to be able to do research.”

View Birdsong’s presentation.

By Sarah Vickery, College of Letters & Science