UTSW Research: COVID-19’s effects, brain-computer interfaces, and more
Studies investigate virus’s low risk for people with MS, a lifeline for paralysis patients, brain protein receptors, and mRNA links to cancer
Assessing multiple sclerosis symptoms after COVID-19
People with multiple sclerosis (MS) are at an increased risk of infection and infection-related hospitalizations, but a study published in Neurology found that being infected with COVID-19 did not significantly affect the course of the disease. A research team that included members from UT Southwestern Medical Center used data from the North American Research Committee on Multiple Sclerosis Registry that tracks thousands of people with MS.
Surveys showed that about 44% of registry members contracted COVID-19 between spring 2020 and fall 2022. Their responses indicated no significant differences in MS symptoms after they had a confirmed diagnosis of COVID-19, compared with those who did not contract the virus. Among the changes measured with a median follow-up time of 18 months after infection were motor function, bodily pain, cognition, depression, and anxiety.
UTSW researchers who contributed to this study include lead author Amber Salter, Ph.D., Associate Professor and Section Head of Biostatistics and Clinical Informatics in the Department of Neurology; and Samantha Lancia, M.S., Data Scientist. Dr. Salter is also an Investigator in the Peter O’Donnell Jr. Brain Institute.
Building better brain-computer interfaces
Brain-computer interfaces (BCI) could eventually be a lifeline for paralyzed people to interact with the world. These investigational devices harvest electrical signals from the brain through an implanted electrode that can be deciphered to direct a computer cursor or control artificial limbs. However, the software currently used in these systems doesn’t interpret brain signals well enough to control devices at the same level as individuals whose motor skills are intact.
To help solve this problem, a team of researchers including Nader Pouratian, M.D., Ph.D., Chair and Professor of Neurological Surgery at UT Southwestern, applied a form of machine learning called a convolutional network. The algorithm they developed, the feature extraction network (FENet), significantly improved the ability of three tetraplegic volunteers to control a cursor on a screen. The study, published in Nature Biomedical Engineering, notes that FENet could be readily used with different datasets, in different brain areas, and in different individuals, suggesting broad applicability for BCI.
Dr. Pouratian is also an Investigator in the Peter O’Donnell Jr. Brain Institute.
Shedding light on structure of certain receptors in brain
Type A GABA (GABAA) receptors are proteins responsible for controlling brain activity and are major drug targets for epilepsy, depression, anxiety, sleep disorders, and anesthesia. These receptors consist of five-part combinations of 19 subunits, so there is a vast array of possible GABAA receptor assemblies. Although studies in rodents and from cell culture have suggested only a small number of GABAA assemblies in humans, the structures from human tissue have been unknown.
Using cryo-electron microscopy on the brain tissue of epilepsy patients, researchers from UT Southwestern and the University of California San Diego collected structure images of so-called native human GABAA receptors for the first time. Their research, published in Nature, found that at least 12 GABAA assemblies exist in human brains, and 3D maps of their structures were then created. Further analysis revealed unexpected binding of two epilepsy drugs on a GABAA assembly type and previously unknown interactions with other proteins. Insights from these findings could be used to develop GABAA-targeting drugs.
UTSW researchers who contributed to this study are senior author Ryan Hibbs, Ph.D., Adjunct Associate Professor of Neuroscience; Bradley Lega, M.D., Associate Professor of Neurological Surgery, Neurology, and Psychiatry; and Haley Moore, B.S., neuroscience graduate student in the Perot Family Scholars Medical Scientist Training Program and member of the Lega Lab and the Konopka Lab. Dr. Lega is an Investigator in the Peter O’Donnell Jr. Brain Institute.
RNA-modifying protein mutations linked to cancer
One way that cells regulate whether genes produce proteins, and how much, is by modifying the molecule messenger RNA (mRNA) after it’s been transcribed – or copied – from DNA. The most common type of mRNA modification is a molecular tag known as N6-methyladenosine (m6A), produced by a protein complex, METTL3-METTL14.
Several cancers have been linked to METTL3-METTL14 overexpression, which causes increased m6A in mRNAs throughout the body. Although researchers have known that the most common mutation of the METTL14 gene derived from cancer patients is found at residue R298, how this mutation contributes to their disease was unknown.
In research published in Science Advances, a team led by UT Southwestern researchers showed that this mutation caused METTL3-METTL14 to preferentially tag sections of mRNA that bear a specific sequence, GGAU. That in turn altered the production of proteins encoded by genes with this sequence – many of which are in known cancer-related molecular pathways. The study authors suggest that these findings could lead to new cancer treatments for patients carrying this mutation.
Researchers from UTSW who contributed to this study include corresponding author Yunsun Nam, Ph.D., Associate Professor of Biochemistry and Biophysics; first author Chi Zhang, Ph.D., Assistant Instructor of Biochemistry; Hao Zhu, M.D., Professor in Children’s Medical Center Research Institute at UT Southwestern, Internal Medicine, and Pediatrics, and co-Leader of the Development and Cancer Research Program in the Harold C. Simmons Comprehensive Cancer Center; Bret Evers, M.D., Ph.D., Assistant Professor of Pathology and Ophthalmology; Chao Xing, Ph.D., Professor in the Eugene McDermott Center for Human Growth and Development, the Lyda Hill Department of Bioinformatics, and the Peter O’Donnell Jr. School of Public Health; Ashwani Kumar, M.S., Computational Biologist; Brijesh B. Khadgi, Ph.D., Senior Research Associate; and Robyn L. Scott, B.S., Meng-Hsiung Hsieh, Ph.D., and Xunzhi Zhang, B.S., Graduate Student Researchers.
Drs. Nam and Xing are also members of the Simmons Cancer Center.
About UT Southwestern Medical Center
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty members have received six Nobel Prizes and include 25 members of the National Academy of Sciences, 24 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 3,200 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 120,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 5 million outpatient visits a year.