IRP Research Hints at Potential of Genomic Technologies to Predict Patient Outcomes
Our genes certainly have a huge influence over our risk for disease, but they don’t operate in a vacuum. Rather, they’re decorated with numerous molecular tags like a bejeweled bracelet, and these ‘epigenetic’ markers affect how genes behave. A recent IRP study revealed differences in certain epigenetic markers that may one day help doctors more effectively treat patients with the autoimmune disease known as lupus.
When IRP graduate student Pilar Alvarez Jerez looked at the results of a recent experiment, she noticed that when a particular genetic variant is present in a gene called GBA1, it causes a change in the gene's activity. The GBA1 variant, which is associated with Parkinson’s disease and Lewy body dementia, was discovered last year in people of African ancestry by researchers at NIH’s Center for Alzheimer's and Related Dementias (CARD). It appears to suppress the gene’s ability to make a functional version of an enzyme that helps brain cells recycle their proteins.
“This was an interesting finding, but it still didn’t answer how the variant was functioning to lower enzyme activity,” Pilar says.
Scientist Honored for Discoveries About DNA Replication
Our cells’ ability to create more of themselves is crucial for many aspects of health, but a cell without DNA can’t do all that much. For that reason, perhaps the most crucial step in cell division is the replication of DNA. IRP Distinguished Investigator Thomas Kunkel, Ph.D., has spent his career trying to understand DNA replication, what happens when the process goes wrong, and what influences the likelihood of mistakes. Earlier this year, he was elected to the National Academy of Sciences (NAS) in recognition of his extensive contributions to this field.
Catching Up With Former NIH Director Francis Collins
It has been 20 years since researchers around the world successfully mapped most of the roughly 20,000 genes that make up the human genome. Former NIH Director Francis Collins, M.D., Ph.D. led the Human Genome Project through most of its 13-year progression and continues to push the limits of genetics today. As we celebrate National DNA Day on April 25, the 71st anniversary of the publication of DNA’s double-helix structure, we took some time to catch up with Dr. Collins and learn what he’s been up to since he stepped down as NIH Director in December 2021.
The dozen or so researchers in Dr. Collins’s lab focus on the role of genes in a variety of diseases, ranging from conditions caused by rare mutations in single genes to common ailments influenced by the interplay of hundreds of genes, lifestyle behaviors, and environmental factors. His two main research interests are type 2 diabetes and Hutchinson-Gilford progeria syndrome, a rare disorder that causes exceptionally rapid aging in children.
Sequencing the Human Genome Sparks Transformation in Medicine
Few people can say they got in on the ground floor of a foundational achievement in science, but that’s where Eric Green, M.D., Ph.D., Director of NIH’s National Human Genome Research Institute (NHGRI), found himself when he began his career. It’s no wonder, then, that he was elected to the prestigious National Academy of Medicine (NAM) in October 2023.
Thirty four years ago, as a newly minted physician-scientist, Dr. Green joined the Human Genome Project, an initiative that had among its leaders former NIH Director Francis Collins, M.D., Ph.D. The initiative aimed to determine the order of the roughly 3 billion DNA building blocks, called nucleotides, that constitute the genetic blueprint for building and operating our bodies. Today, Dr. Green leads the NIH Institute that was established to lead NIH’s contribution to that ambitious endeavor, overseeing the investigation and application of information and technologies that drive the application of genomics to modern-day medicine.
Andrew Singleton and Ellen Sidransky Lauded for Genetics Research
Throughout history, some of the most important insights about devastating illnesses have come from identifying genes that contribute to them. Parkinson’s disease, a neurological condition that robs patients of the ability to move, is just one example of this pattern — and one that IRP researchers have made critical advances on in recent years.
Reflecting the IRP’s groundbreaking research on Parkinson’s disease, in September, IRP senior investigators Ellen Sidransky, M.D., and Andrew Singleton, Ph.D., were awarded the prestigious Breakthrough Prize for their research on the genetic causes of the illness. The world’s largest scientific award, the Breakthrough Prize honors “transformative advances toward understanding living systems and extending human life.” Each year, one award in the Life Sciences category is reserved for research on Parkinson’s and other neurodegenerative disorders. Dr. Sidransky and Dr. Singleton, along with a third Parkinson’s researcher, Thomas Gasser, M.D., Ph.D., at the University of Tübingen in Germany, will share the $3 million prize.
IRP Researchers Leave Jargon Behind for Three-Minute Talks Competition
Scientific research is often said to take place in an “ivory tower” — not exactly an image associated with accessibility, trust, or empathy. Yet it is essential that members of the public be able to understand the work that researchers devote their lives to.
In recognition of that need, dozens of IRP postbacs, graduate students, and postdocs participate each year in NIH’s Three Minute Talks (TmT) competition. On June 22, this year’s eleven finalists offered clear and concise descriptions of their efforts to unfold the mysteries of proteins’ shapes, discover the lethal role of inflammation in infections, repackage cancer therapies to enhance their effectiveness, and much more.
Mouse Study Demonstrates Promise of New Therapy for Rare Genetic Conditions
If you ask a scientist how old you are, you may be surprised to get a different answer depending on who you’re talking to. That’s because age can be measured both ‘chronologically’ — in terms of time — and at a cellular level. Indeed, certain genetic mutations cause cells to age faster, leading to a host of health problems. Fortunately, a recent IRP study performed in mice suggests that boosting levels of a specific molecule could help alleviate some of those patients’ symptoms.
NIH Archives Document the Tremendous Importance of Female Scientists
Women’s History Month is celebrated every March, and women scientists have undoubtedly made invaluable contributions to IRP research over the course of NIH’s history. Despite this, women still remain under-represented in biomedical science at NIH and elsewhere today, prompting the IRP to make supporting the careers of female researchers an important priority. While NIH works to rectify the gender imbalance in scientific research, it’s important to take time to celebrate the many women who, even when confronted with significant historical obstacles, have made a name for themselves in the lab and on the pages of scientific journals. Join me in taking a look through the archives of the Office of NIH History & Stetten Museum to learn about some of the many women scientists who have been at the forefront of science and administration at NIH.
IRP Research Hastens Development of First Treatment for Genetic Muscle Condition
An old medical adage warns doctors that when they hear hoofbeats, they should first think of horses, not zebras. After all, when someone comes into the hospital with a cough, the most likely explanation is something mundane like the flu. However, some patients truly are medical zebras, affected by a disease that afflicts very few others.
IRP senior investigator Marjan Huizing, Ph.D., has learned quite a bit about those zebras since arriving at the National Human Genome Research Institute (NHGRI) as a postdoctoral fellow in 1998. To help commemorate Rare Disease Day today, Dr. Huizing spoke with the “I Am Intramural” blog about her research on an array of ailments linked to a small sugar molecule called sialic acid, some of which are extremely rare.
