2020 June

June 2020

MARC/IMSD awarded grant to continue training diverse scientists

June 3, 2020 By Jerome Duggan in Research Tags: MARC/IMSD, NIH

New funding changes some structure to program

By Jerry Duggan | Bond LSC

Mizzou was always near the top of Olivia Warner’s list for Ph.D. programs.

Its renowned psychological sciences program, sound training in Warner’s specialty of addiction and supportive, collaborative atmosphere that she didn’t see at other places made it a top choice on paper.

But she was not introduced to her most formative program in terms of professional development until she had already moved across the country from Arizona to mid-Missouri. Within her first month, Warner learned of the Maximizing Access to Research Careers/Initiative for Maximizing Student Diversity (MARC/IMSD) program.

“I found out about IMSD right away, and I’m glad I did,” Warner said. “Without this program, I would have had a tougher time networking on campus, and wouldn’t have picked up a lot of the skills that I have today.”

MARC/IMSD is a federal program that partners with universities to identify and train the next generation of researchers in biomedical and behavioral sciences. It provides research, mentoring, academic and social support, and professional development to help them along the way to doctoral degrees that will lead them to diversify the workforce. These underserved students include minorities from different ethnic and racial backgrounds, those with disabilities, students from low socioeconomic backgrounds and first-generation college students. The program gives them a helping hand in graduate school.

“Evidence says teams from diverse backgrounds approach problems differently and, ultimately, better in terms of solutions than teams of individuals from similar backgrounds,” said Dr. Mark Hannink, director of MARC/IMSD, Bond Life Sciences Center principal investigator and Biochemistry faculty member. “Data drives the National Institutes of Health’s recognition that entire research enterprises benefit from different perspectives and approaches.”

For 20 years, Mizzou was the recipient of an MARC/IMSD grant from the National Institutes of Health (NIH), that provided mentored research training and professional development to both undergraduate and graduate students. Hannink said that while the mentoring and professional development will continue, there will be changes in MARC/IMSD’s structure with the new grant. The most significant change is that the undergraduate and graduate training programs are now separated into two different grant-funded programs. The graduate MARC/IMSD program, which will become a T32 training program, has recently received $2.2M in funding from NIH to support training of 25 students over five years. A number of units at MU, including the School of Medicine, College of Veterinary Medicine, College of Engineering, College of Food, Agriculture and Natural Resources, the Division of Biological Sciences and the Graduate School, have provided funding to support training of at least 10 additional students. The MARC/IMSD program is truly a partnership between NIH and MU that will have a significant impact on diversity in biomedical research.

“This is more than just a scholarship,” Hannink said. “It’s a training program, in which students develop three different areas of expertise that our students need to develop to become successful scientists: professional, technical and operational skills.”

These objectives include increasing the percentage of underrepresented minorities in participating biomedical predoctoral students to 20% from 16%, to improve the Ph.D. completion rate for such students to 90% from its current 84%. An end goal is that 30% of trainees obtain external fellowships during their time in the program.

While MARC/IMSD provides two years of financial support to participants, its key focus is to foster professional development programs, workshops and support mechanisms to ensure that students in the program have whatever they need to succeed.

Coming out of Arizona State University with degrees in Psychology and Human Development, Warner worked full time for three years and volunteered in a lab, researching the ways in which contextual and interpersonal factors influence alcohol use motives and subsequent problematic use.

Despite significant research experience, Warner’s transition into the six-year clinical psych sciences Ph.D. program would have been much more difficult if not for MARC/IMSD.

“I was connected with Dr. Hannink pretty much immediately after I arrived on campus, and surrounded with people in the program that had a lot of shared experiences with me,” she said. “The program provided extra support and a sense of togetherness for us, which is really important since a lot of us are underrepresented in Ph.D. programs. It really helps to be around a group of people you can relate to and connect with.”

Under the new grant, much of the mentoring aspect of the program will remain the same, but the new format will be much more explicit in terms of the specific training activities used to develop said technical, operational and professional skills.

In addition to moral support and togetherness, MARC/IMSD aims to equip participants with academic skills. For Warner, who just completed her second year of the program, this meant taking a professional development class taught by Hannink. The class included a segment on public speaking which was especially beneficial for Warner.

“Having public speaking and presentation skills is a large part of any successful researcher’s skill set, so it was really helpful for me to be able to develop those skills early on in the program,” Warner said.

Participants also complete rotations in other labs besides their own as part of the program in order to broaden their knowledge about all areas of research, and are given opportunities to network with experts in the field. Many cycle through labs within Bond LSC.

“The next generation of researchers need to have exposure to disciplines outside their degree, to be able to talk with people doing research that’s very different than their own and collaborate effectively,” Hannink said.

Warner wants to be able to continue her research in some capacity for the rest of her career, so being a well-rounded graduate able to face any challenges thrown at her is invaluable.

“Everything I’ve been a part of in this program, from the professional development class, to being exposed to areas of research I might not have otherwise known anything about, has been very beneficial,” she said.

The science community as a whole reaps benefits from this development.

“Any research effort is more effective if it’s inclusive and brings different perspectives and approaches to the problem, and that’s how the skills IMSD teaches really translate long term into a better biomedical workforce.”

MU received a National Institutes of Health five-year grant for $2,228,008 to continue its focus on minority graduate student development in biomedical and behavioral sciences. This grant started February 1, 2020.

Studying Drug Resistance, One Connection at a Time

June 1, 2020 By Becca Wolf in Research Tags: drugs, virology

Kinjal Majumder | photo by Mariah Cox, Bond LSC

By Becca Wolf | Bond LSC

Where you are creates opportunities.

The structure and placement of labs encourages researchers to collaborate and talk to each other and often, connections and friendships are formed.

For Kinjal Majumder, a virologist and postdoctoral fellow in the David Pintel lab at Bond Life Sciences Center, that has meant bouncing many ideas off friends and colleagues from neighboring labs. Little did he know that one connection would lead him to interesting findings in a field outside of virology.

Those results may help make progress toward understanding the machinery behind drug resistance and toxicity in the body.

“The big picture is that it will help future studies on how drugs are metabolized by our body,” Majumder said.

The connection started with Andrew Huber, the first author of the paper, who completed his Ph.D. while in the lab of Dr. Stefan Sarafianos at Bond LSC. He graduated two years ago, moved to the lab of Dr. Taosheng Chen at St. Jude Children’s Research Hospital (SJCRH) in Memphis, Tenn. and began his postdoctoral work.

Dr. Chen’s lab focuses on mechanisms of cellular drug metabolism, one of which functions through the pregnane X receptor (PXR) protein.

PXR is found in the liver and is activated by drugs and other substances in the blood. Once activated, it binds to DNA and activates genes responsible for detoxifying the system. However, this system often leads to metabolism and reduced efficacy of administered drugs such as chemotherapies and antibiotics.

“When Andrew was in the Sarafianos lab, we’d talk science often and we collaborated on how different viral proteins bind to host and virus DNA, and how this can aid viral life cycles,” Majumder said, “When he moved on to his postdoctoral work, he saw that he can start applying similar techniques to study how the liver metabolizes toxins. So that’s when we set up this collaboration to pursue these things together.”

Majumder studies how viral DNA and proteins interact in virus-infected cells. One technique he uses is called chromatin immunoprecipitation assay (ChIP) which determines where proteins of interest can bind to DNA molecules. Majumder freezes protein and DNA that are interacting together in the process and he pulls that complex down with an antibody. “It’s like going fishing,” he said.

In order to apply ChIP and other techniques to study PXR signaling, Majumder drove down to SJCRH in Memphis to work with Huber on these assays.

Once in Memphis, Majumder and his collaborators worked and conducted experiments around the clock, but they also found time to explore the city and have fun.

“We go into lab and try to get done as many experiments as we can,” Majumder said, “And whenever we have a long break we go out on the town. It’s usually a really fun way to go and experience the life and scientific culture of a new place.”

It is a lot to pack into one week, but Majumder and his collaborators make the most of it, finding a way to effectively balance their studies on PXR with soaking up life in Memphis.

Majumder compares PXR to a light dimmer switch. When activated, it “brightens” by increasing drug metabolism, leading to decreased drug efficacy. PXR inhibitors work to “dim” this effect. At St. Jude, Dr. Chen’s group found that of the 434 amino acids that make up PXR, only one mutation is needed to “turn a dimmer into a brightener.”

“We sort of got lucky, we thought that you’d have to make a lot of changes in order to make PXR do something different,” Majumder said, “Without making too many changes — Dr. Chen’s group just switched one thing — and that was sufficient enough to turn it into a brightener. So that was a happy and unexpected outcome.”

Once these results were reviewed, the Cellular and Molecular Life Sciences journal accepted their results and published them this March in an article titled “Mutation of a single amino acid of pregnane X receptor switches an antagonist to agonist by altering AF-2 helix positioning.”

Looking ahead, Majumder and his collaborators hope to make more progress in understanding how drugs are metabolized in the body.

All of this would not have been possible if it wasn’t for the connections Majumder made at Bond LSC a few years ago.

“It was so cool to have this opportunity to collaborate with someone from the LSC that I have collaborated with before and apply our experimental techniques to study a new system,” Majumder said, “It feels very encouraging that now the work can be expanded upon and applied to other systems and settings.”