The biochemistry department participated in the 18th Annual Village Walk for Cancer Research in Hot Springs Village. The walk is a fundraiser for cancer research at WPRCI. Funds from last years walk are currently funding a project addressing drug resistance in lymphoma in Samantha Kendrick‘s lab. Also walking were Stephanie Byrum, Alicia Byrd, and Tung-chin Chiang.
News
Department welcomes new students with picnic
The Biochemistry and Molecular Biology welcomed new GPIBS students to UAMS with a picnic at Allsopp Park. Thanks to students Katie Bronson and Allie Davis for helping with the organization and set up.
Allie Davis and Binyam Belachew receive white coats
Allie Davis, a graduate student in Dr. Paul Miller’s lab, and Binyam Belachew, a graduate student in Dr. Kevin Raney’s lab received their white coats at the UAMS Graduate School’s annual Research Induction Ceremony celebrating Ph.D. candidates who have successfully passed their qualifying exam in the past year. Congratulations Allie and Binyam!
Allie Davis Elected to Two Professional Groups
Allie Davis, a graduate student in Dr. Grover Paul Miller’s lab has recently been elected to two different groups.
Allie was elected to serve on the International Society for the Study of Xenobiotics (ISSX) New Investigator Group. This group comprises promising new investigators (predoctoral, postdoctoral, and new to their careers) that recruit and retain new ISSX members and promote interaction and collaborations between new members and more experienced members to ensure a lively and diverse group for many years to come. Currently, the new investigator group is writing up a conference proceedings paper that covers the ISSX international meeting from this past July.
Allie was also selected to serve on the Drug Metabolism Reviews (DMR) editorial board. Being a predoctoral student, access to many editor friends and colleagues she’s met at conferences and events will help her to learn the editorial process. Allie was selected for this group because she is a promising new investigator who has shown that she is willing and able to communicate and collaborate with scientists across many branches with varying degrees of experience.
Congratulations Allie!
Graduate Student Explores Potential of Handheld DNA/RNA Sequencers in Outbreaks
By Amy Widner
Imagine there’s an outbreak of an infectious disease. Could health officials on the ground harness the power of new handheld DNA and RNA sequencers to monitor outbreaks in real-time and quickly contain them?
This question lies at the heart of research published in the journal Infection, Genetics and Evolution by UAMS Biochemistry and Molecular Biology track graduate student Duah Alkam. She and her advisers from the College of Medicine Department of Biomedical Informatics and the Department of Microbiology and Immunology collaborated with the Arkansas Department of Health to look at specimens collected during a 2016 mumps outbreak in Northwest Arkansas.
It took the Human Genome Project 13 years to complete the first sequence of a human genome in 2003. As sequencers became available for purchase, they were large, expensive and slow.
That has changed. Alkam used a device called the Oxford Nanopore Technologies MinION to sequence each sample in a matter of hours. To offload the data, she simply connected the MinION through a USB port to a laptop.
“You see results on your computer in real time,” Alkam said. “It’s fast, affordable and simple. The idea is that something like this might be useful during an outbreak, especially in a rural setting. If you can quickly identify a strain, you’re that much closer to understanding the origin of the outbreak, which may help contain it and protect the at-risk population.”
The new challenge for scientists is how to interpret the massive amount of data produced by these powerful sequencers. That is where the relatively new field of biomedical informatics comes in.
“Biomedical informatics allows us to look at genomes within a matter of hours and compare them, pinpointing connections and what might be important about these datasets,” Alkam said. “In this way, biomedical informatics is sort of the bridge between raw data and relevant information.”
In this case, Alkam was able to determine the unique characteristics of the specific variation of the mumps virus that was behind the 2016 outbreak. They used a computational technique called immunoinformatics to plot a “family tree” of sorts for the virus.
“We found that it was very similar to a strain that started an outbreak in Massachusetts around the same time in 2016, and it was also related to another strain that spread in Washington state, which may suggest that all three outbreaks originated from the same strain.”
While Alkam’s experiment was not conducted during an active outbreak, she and her advisers believe the results demonstrate great promise for the technique to be applied in the real world. Earlier in 2019, other scientists in the Department of Bioinformatics collaborated with researchers around the world for the first demonstration that the MinION could be used for the rapid genetic sequencing of multiple human viruses.
“The possibility of infectious disease outbreaks in health care settings and communities is something that unites us across the globe. We’re all vulnerable,” said Se-Ran Jun, Ph.D., Alkam’s adviser for the project and an assistant professor in biomedical informatics. “So at UAMS, it’s exciting each time we demonstrate how we can harness the power of new sequencing technology, big data science and analytics, and high performance computing in biomedical informatics to offer solutions.”
The project was funded with a grant to Jun from the UAMS for Translational Research Institute.
Alkam is a student in the UAMS Graduate School’s Graduate Program in Interdisciplinary Biomedical Sciences (GPIBS). Her other advisers are David Ussery, Ph.D., a professor in the Department of Biomedical Informatics; and Mark Smeltzer, Ph.D., a professor in the Department of Microbiology and Immunology.
Maroof Zafar is the visitor of the week at CSHL
Maroof Zafar, a postdoctoral fellow in Alicia Byrd’s lab, was the featured visitor of the week at Cold Spring Harbor Labs when he attended the CSHL Eukaryotic DNA Replication & Genome Maintenance Meeting. Check out the article about him.
Megan Reed and Maroof Zafar present at DNA replication meeting
Megan Reed, a graduate student in Robert Eoff’s lab presented a poster entitled “DNA polymerase kappa modulates glioma cell plasticity in response to DNA damage” at the Cold Spring Harbor Labs Eukaryotic DNA Replication & Genome Maintenance Meeting.
Maroof Zafar, a postdoctoral fellow in Alicia Byrd’s lab presented a poster entitled “Human DNA helicase B protects stalled forks from degradation after replication stress” at the Cold Spring Harbor Labs Eukaryotic DNA Replication & Genome Maintenance Meeting.
August publications
Davis LE, Shalin SC, Tackett AJ.
Cancer Biol Ther.
PHF19 promotes multiple myeloma tumorigenicity through PRC2 activation.
Ren Z, Ahn JH, Liu H, Tsai YH, Bhanu NV, Koss B, Allison DF, Ma A, Storey AJ, Wang P, Mackintosh SG, Edmondson RD, Groen RWJ, Martens AC, Garcia BA, Tackett AJ, Jin J, Cai L, Zheng D, Wang GG.
Blood.
Glazko G, Zybailov B, Emmert-Streib F, Baranova A, Rahmatallah Y.
PLoS One
Eugene Nyamugenda Student Highlight
Eugene is a Ph.D. Student in his 5th year in the Biochemistry and Molecular Biology Department in the laboratory of Dr. Giulia Baldini.
He has a B.A. in Biochemistry and Molecular Biology from Hendrix College.
Research Interest Statement
The hypothalamus plays a central role in maintaining healthy energy homeostasis. The arcuate nucleus (ARC) of the hypothalamus receives anorexigenic signals from the periphery mediated by increased circulating leptin and insulin, which bind to receptors expressed by proopiomelanocortin (POMC) neurons in the ARC. When activated, POMC neurons release α-Melanocyte stimulating hormone (α-MSH). In the paraventricular nucleus (PVN), α-MSH binds to the melanocortin-4 receptor (MC4R) to signal decreased food intake and increased energy expenditure. Single-minded-1 (Sim1) neurons in the PVN include the population of MC4R neurons. My research uses mice to study the effect of obesity by a high-fat (HF) diet on the PVN neurons expressing Sim1 transcription factor and MC4R. When mice are fed HF diet, they have increased body weight as a result of increased caloric intake. We found that exposure to HF diet induces loss of Sim1 neurons in the PVN and, in male mice, loss of POMC neurons and α-MSH abundance. Because there are no reliable commercial antibodies that can detect MC4R, we generated a knock-in mouse line expressing HA-tagged MC4R (MC4R-HA) by using CRISPR/Cas9 technology to detect MC4R protein. We found that HF diet induces injury to MC4R neurons in the PVN as indicated by loss of MC4R protein, decreased mitochondrial abundance, and mitochondrial network size. The data suggest that HF diet induces loss of MC4R protein rather than of MC4R neurons, suggesting that expression of MC4R could be a target for anti-obesity therapy.
Something Notable about Time as a Graduate Student
Overall my time in graduate school has been excellent. I would say that I happened to fall into the right group of people. The life lesson I learned is never to translate a joke. The chances are either the joke is not funny, none understands it, or you will offend someone.
Career Goals
I want to do a postdoctoral fellowship for a few years and look for opportunities in biotech and pharmaceutical companies.
Experiment or Technique You Would Most Like to Do
I like to do many experiments. I love making DNA constructs. It excites me. If my labmates wanted to subclone anything, I would volunteer to do it.
Fun fact
When I grew up, my mother treated every ailment with a specific type of food (she still does). When I got sick in boarding school, I asked permission to go home. She would cook food for me, and the next day I would feel better and go back to school. Food is still my over-the-counter medicine today. If you see me sick, the first treatment to give me is food (enough of it).
Publications
Nyamugenda E, Cox AB, Pierce JB, Banning RC, Huynh ML, May C, Marshall S, Turkal CE, Duina AA. Charged residues on the side of the nucleosome contribute to normal Spt16-gene interactions in budding yeast. Epigenetics. 2018; 13(1):1-7. doi: 10.1080/15592294.2017.1418132. Epub 2018 Feb 8. PMID: 29271283
Nyamugenda E, Trentzsch M, Russell S, Miles T, Boysen G, Phelan KD, Baldini G. Injury to hypothalamic Sim1 neurons is a common feature of obesity by exposure to a high-fat diet in male and female mice. J Neurochem. 2019 Apr; 149(1):73-97. doi: 10.1111/jnc.14662. Epub 2019 Feb 11. PMID: 30615192
Awards
Rwanda Presidential Scholarship
Robert Eoff, Ph.D., Receives $1.2 Million Grant from National Science Foundation
Researcher Robert Eoff, Ph.D., has received a $1.2 million grant from the National Science Foundation to continue his work at the University of Arkansas for Medical Sciences (UAMS) on DNA damage, cell replication and its implications for diseases like dementia, ALS and cancer.
Eoff is an associate professor in the Department of Biochemistry and Molecular Biology in the UAMS College of Medicine and a member of UAMS’ Winthrop P. Rockefeller Cancer Institute. Julie Gunderson, Ph.D., assistant professor of physics at Hendrix College in Conway, is collaborating with Eoff on the project. The four-year grant will also support graduate student training at UAMS and undergraduate trainees at Hendrix.
Eoff’s research team studies what happens when DNA damage is not repaired in a timely manner and ends up blocking the mechanics behind how copies of new cells are made. Specifically, he studies the effect of large amounts of guanine in DNA sequences, which can form unusual structures called G-quadruplexes (G4).
“Imagine trying to copy a document containing over six billion letters in the span of a few hours,” Eoff said. “Now imagine finding that the text contains many words like ‘Mississippi,’ ‘Czechoslovakia,’ ‘Oberschleissheim’ and ‘Solgohachia.’ Even though you’re on a tight schedule, you might have to slow down a bit when you come to those tricky words.
“As it turns out, this is probably a good analogy for what happens when enzymes involved in DNA replication encounter certain sequences that contain an abundance of guanine bases,” Eoff said.
Errors in these G4 sequences can lead to changes in the genome that are associated with human disease. For example, neurological diseases such as frontotemporal dementia, amyotrophic lateral sclerosis (ALS), and the intellectual disability fragile X syndrome have all been linked to dysfunctional G4 maintenance.
There is also a substantive and growing body of literature linking G4 to the biology of cancer and cancer therapies. Many cancer-related genes are controlled by G4 motifs, and chromosomes in tumor specimens tend to be broken more frequently near G4 sites than other DNA sequences.
However, scientists do not fully understand how these errors occur.
For this specific grant, Eoff will study the role of a special enzyme called Rev1 in copying G4 sequences. Rev1 is a DNA polymerase — an enzyme that catalyzes synthesis of new strands of DNA.
“Successful completion of this research will give us a better understanding of how G4 replication errors occur and how they might have come about in the first place,” Eoff said. “Hopefully, this will give us new insight into replication barriers, which cause a wide range of issues in humans and other species, as a first step toward putting this greater understanding to use in the form of new treatments and therapies.”