Contact:
Anthony Lane
410-455-5793
alane@umbc.edu

The goal of personalizing medical treatment on a genetic level is complicated by the human genome’s size: It contains about 22,000 genes that serve as blueprints for an even greater number of proteins needed to make cells function. Linking diseases and disorders to individual protein defects — and underlying genetic mutations — is a monumental and challenging task.

Researchers at the University of Maryland, Baltimore County (UMBC) are simplifying this task and accelerating progress toward personalized medicine by offering a new tool that catalogs these defects as they appear in the roughly 4,000 protein domains that recur in proteins.

The Domain Mapping of Disease Mutations (DMDM) database, bioinf.umbc.edu/dmdm, enables researchers to look for new links between diseases and therapeutic approaches by providing a map of the flaws that show up in what amounts to a “parts warehouse” for proteins.

“We are trying to change from a gene-centric perspective to a domain-centric view,” says Maricel Kann, an assistant professor in UMBC’s Department of Biological Sciences. “This approach will provide valuable perspective as researchers grapple with the vast amount of data that gene-sequencing technology has made available.”

Kann’s multidisciplinary research team — consisting of undergraduates and graduate students — described the database in an article published in August in the journal Bioinformatics. Updated this month, DMDM now tracks more than 120,000 mutations drawn from the three primary databases tallying research in genetic diseases, mutations and protein structures.

The DMDM database currently receives about 1,200 visits a week. Visitors can search by disease, gene, protein or domain. At each level, the database shows the location of known mutations. For domains, the database shows the number of mutations found in each location, with information about the associated proteins.

Domains are the basic functional units of proteins. Highly conserved throughout evolution, each domain gives a protein a new capability, such as the ability to bind to DNA or to catalyze a specific reaction.

To build the DMDM database, UMBC researchers downloaded the known disease-causing point mutations (a point mutation causes a change from one amino acid to another) from several public databases. They then mapped the mutations to positions within individual proteins and protein domains, finding that more than 75 percent of the disease mutations fall within protein domains.

This finding shows that domains are critical to the proper functioning of proteins: When a mutation falls within a protein domain, the protein’s function is often disrupted and disease can result.

As more and more individual genomes are sequenced, more new mutations will be identified. Researchers can use DMDM to check if a mutation falls within a domain to see if it is likely to disrupt protein function. Researchers can also check if a mutation in a certain position within the domain has previously been linked to disease. Ultimately, mutation “hotspots” within domains could be targeted by pharmaceutical companies for drug development.

A screenshot from the database is below:

Contact:
Dinah Winnick
Communications Manager
University of Maryland, Baltimore County (UMBC)
410-455-8117
dwinnick@umbc.edu

Faculty of UMBC’s Center for Aging Studies, affiliated with the Department of Sociology and Anthropology, have received several large grants from the National Institute on Aging to support groundbreaking research in recent months, including three beginning this semester.

“Autonomy in Assisted Living: A Cultural Analysis,” led by PIs Ann Christine Frankowski and Robert L. Rubinstein, is a four-year grant to study autonomy in six diverse assisted living settings, which provide residential and functional assistance to primarily older adults through a person-centered, consumer-oriented, social model of care. Researchers have demonstrated that older adults’ sense of autonomy – expressed as independence, choice or control – is integral to their health and well-being. The research team will examine how autonomy, a core American value and a key component of assisted living philosophy, is defined, experienced and negotiated by assisted living residents. This ethnographic research will inform policy and practice on how assisted living can provide an environment resulting in a better quality of life and care for the increasing number of adults living longer and moving into senior housing.

“Generativity in the Lives of Older Women” (GLOW) is a four-year project led by PI Robert L. Rubinstein and co-PI Kate de Medeiros aimed at better understanding how older women without children invest themselves in future generations. People often wrongly assume older women are mothers and/or grandmothers. In reality, approximately 20% of people 65 and over in the U.S. were “childless” in 2011—a figure that is expected to grow to 30% in 2030. GLOW researchers will interview 200 women to explore their views on the meaning that not having children has had in their lives; talk about ways they have influenced future generations through volunteerism, teaching, passing along personal objects and other creative activities; and discuss their plans for managing future health care needs, which might include family caregiving. This study will allow us to learn more about an important yet often overlooked population with an eye to helping service organizations and policymakers rethink assumptions about family structure in older age. GLOW is accompanied by a supplemental grant focusing on older Russian women who immigrated to the U.S. after the fall of communism.

Department chair J. Kevin Eckert and co-PI Brandy Harris-Wallace received a Research Supplement to Promote Diversity in Health-Related Research for “Stigma and the Multicultural Workforce.” This project will focus on cultural differences among direct care workers, their experiences of stigma and their own stigmatizing attitudes and behavior toward others in assisted living settings. The researchers will develop and pilot a survey instrument to measure these experiences, attitudes and behaviors, which could be used in the future to identify actual and potential conflict areas and develop training programs to address stigma in direct care work.