For more than ten years, PSC has been reaching out to minority-serving institutions (MSI) with bioinformatics training. This year, the annual MARC (Minority Access to Research Careers) program at PSC began with a nine-day workshop in June. The interns, who were undergraduates, graduate students, and even a faculty member this year, stayed for a seven-week internship where they applied their new bioinformatics skills to a research question.
Although they’ve all left for home, we could not forget this bunch. We want to brag about the interesting research that the interns did with their PSC mentors, Dr. Hugh Nicholas, Alex Ropelewski, and Dr. Troy Wymore. So, in the next few posts, we’ll present the the 2012 MARC summer interns and their projects. First up, the undergraduates:
Angela McClendon will be a senior at Jackson State University this fall, majoring in chemistry and biology. That’s a great background for her intended career in pharmacy, and that ties in nicely with her MARC project. Working with Troy, she studied sensor proteins that contribute to antibiotic resistance in bacteria.
Specifically, she was hoping to pinpoint some differences between a protein known as BlaR (pronounced blah-are) and β-lactamases, enzymes which attack β-lactam antibiotics. (The β-lactam class of antibiotics contains penicillin derivatives and cephalosporins, among others.)
The sensing proteins, like BlaR, are structurally very similar to β-lactamases. So why does BlaR have very little effect on β-lactam antibiotics, when β-lactamases destroy them?
Using phylogenetic analysis, Angela was able to pinpoint differences in the amino acid residues of BlaR and β-lactamases that most distinguish the proteins from the enzymes. She had no experience in bioinformatics before this summer. “I learned a lot about bioinformatics,” she says. “I learned how to align sequences, how to annotate a protein structure, how to make a phylogenetic tree.”
Angela also found many differences between Jackson, Mississippi and Pittsburgh. One difference in particular really makes her shake her head: “We do not ride our bikes in traffic,” she laughs.
Alexandra Medina, a senior studying microbiology at the University of Puerto Rico, Mayagüez campus, was also looking at the problem of antibiotic-resistant bacteria. Her adviser there, Dr. Carlos Rodriguez Minguela, is interested in GES-21, a β-lactamase that was found in waste waters in Puerto Rico. This summer Alexandra hoped to identify residues in GES-21 and other closely related β-lactamases that can be useful to predicting their functionality.
With no background, though, she first had to learn something about bioinformatics. “These two months have been hard, but I have learned a lot,” she says.
She started by finding enzymes with similar sequences to GES-21, and after using several software packages to eliminate extraneous sequences, align the remaining sequences, find patterns among them, and then refine the alignment, she was able to produce a phylogenetic tree showing evolutionary relationships between GES-21 and other β-lactamases.
She was also able to identify several amino acid residues common to the group containing GES-21 and a closely related group. (β-lactamases are grouped based on nucleotide and amino acid sequences.) The residues that she found are critical for the specific functionality of those groups and distinguish those groups from other groups of β-lactamases.
This can be really useful in fighting antibiotic resistant bacteria. GES-21, says Alexandra, makes bacteria resistant to a class of antibiotics called carbopenames.
“[Carbopenames] are used in hospitals and medical treatment as a last resort,” she says, because they are unaffected by most of the enzymes produced by bacteria. GES-21, however, is an exception; it attacks carbopenames and reduces the antibiotic’s effectiveness. Finding out what makes enzymes like GES-21 different could lead to a way to counteract its effect on carbopenames – extremely useful information in a clinical setting.
Has she learned anything besides bioinformatics in her stay here? “Oh my, everything!” she says. “I have never spent so much time alone, so I have been trying to get around on the buses – try to venture out myself , expand my boundaries, be a little bit more independent.” At least one thing she learned will surprise her parents. “I’ve learned to cook a little bit. Now I can make chicken and rice!”
Charnelle Smoak had to overcome not only a change of environment but also a change, essentially, in language. A junior studying computer science at North Carolina A & T University, she had little background in biology. “When I first came here, I had to figure out what multiple sequence alignment was! It was confusing for me at first, but when they started speaking Python (a computer programming language), I understood that.”
Her project, mentored by Alex Ropelewski, was to write a better multiple sequence alignment (MSA) program. “The method is fairly simple,” she says. “I break the alignment up based on motifs. Motifs are conserved residues that the MEME program – that’s the one that I’m using – picks out, and these residues are important because they’ve been conserved [through the evolutionary process] for functional or structural tasks.”
Once the motifs are identified, those already aligned by the MEME program are set aside. Charnelle’s program does a separate alignment on what remains. Then those new alignments are stitched back together around the MEME motifs, to create a better MSA.
“I thought I would just learn a whole bunch of biology from this internship, but I’ve learned a lot. I learned some things through the workshop that have nothing to do with my project, but are useful to me as a computer scientist,” like Unix and SQL and some intricacies of Python, she says.
She thinks of computer science as a key. “In computer science, you learn a lot more than just computer science, because you are going to have clients of all different types. You might have a client that wants a program that does calculus, there might be one like this one that does biology, whatever it is, you have to learn at least a minimum [about the subject matter] to make the program to its specifications.”
She definitely plans to go to graduate school. “I want to become Dr. Smoak,” she says.
And apparently a crash course in bioinformatics wasn’t enough new skills for one summer. One of the other interns also introduced her to salsa dancing. “So I’ve been taking classes and learning how to salsa. And I’ve been pleasantly surprised because I didn’t think I would be able to pick up any rhythm, I can’t dance whatsoever. But the instructor said, ‘You’ve improved so much.’ And I can actually do a little dance and almost look like a professional.”
Taylor is a senior applied math major at North Carolina A&T. Her biology was a little rusty; no surprise, given that her last biology class was in 9th grade. She had to do a lot of research on her own to come up to speed. “I read a lot of the papers that Dr. Hugh gave me, and I did a lot of Googling, and I used the Encyclopedia Britannica online,” she says.
Then her intended project changed at the last minute. Hugh and Dr. Gregory Goins, of the NC A&T department of biology, were planning to have Taylor develop a tool for biologists that would help categorize sequences into orthologs or paralogs. “They found out maybe two weeks before I got here that someone had developed a package to do similar things,” Taylor says. “So [my project] evolved into trying to use that package to see what kind of results it gives.”
The package that Taylor evaluated, bios2mds, can read in multiple sequence alignment files, calculate distance matrices, and perform metric multidimensional scaling. Her testing indicates that bio2mds can be a useful tool.
“What I have been doing is to look at the results it gives, and comparing it to the phylogenetic tree. It gives you really good results,” she says. “I think the largest alignment I’ve done is a little over 200 sequences. It gives you groups that are all together on the phylogenetic tree. It’s a really accurate tool.”
Taylor plans to continue her education into graduate school, hoping to go straight into a PhD program. Although she’s not certain in what area, she thinks she would like to continue with applied mathematics.
Being in her hometown, Taylor should have had no surprises this summer, right? Not so. “I was telling the other interns that I lived in Pittsburgh my whole life, I went to St. Agnes School, down 5th Ave. (two miles from the PSC), and for high school I went to Oakland Catholic right on Craig Street (the same street that PSC is on, and just 3 blocks away) and I never knew this building existed. In high school, we were all up and down this entire street, but I never paid [the PSC building] any attention, that whole time. I thought that was pretty funny.”
UPDATE: Congratulations to Taylor for winning an award for best poster presentation at the 2012 AGMUS Research Symposium. Way to go, Taylor!
In the next post we’ll focus on the rest of the MARC interns and their research, including creating tastier guinea fowl, a clam with an unusual hemoglobin that carries sulfur instead of oxygen, and a family of bacterial proteins that may play an anti-aging role (at least in yeast). Stay tuned!