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Institute News

Common gut bacteria have a taste for tungsten

AuthorGreg Calhoun
Date

January 9, 2025

A bacteria linked to longevity was found to feast on lactate only when the meal contains the metallic side dish

In a new paper published December 30, 2024, in PNAS, study coauthor Dmitry A. Rodionov, PhD, research assistant professor in the Immunity and Pathogenesis Program at Sanford Burnham Prebys, and colleagues, studied how Eubacterium limosum contribute to a healthy human gastrointestinal microbiome by metabolizing lactate.

Lactate or lactic acid is a normal byproduct that is created as our cells generate energy. Lactate can be found in the guts of healthy adults at low concentrations because microbes such as E. limosum make a meal of much of it, preventing the abnormal accumulation sometimes found in patients suffering from ulcerative colitis and other gut-related disorders.

Rodionov and his colleagues examined how E. limosum bacteria break down lactate into short-chain fatty acids (SCFAs) and were surprised to find that the metabolic process depends on two tungsten-containing enzymes.

The authors suggest that their findings are a tipoff that tungsten might be an overlooked micronutrient in the human gut microbiome and may contribute in unappreciated ways to overall human health.

Institute News

Mutations in protein receptor gene linked to Alzheimer’s disease

AuthorGreg Calhoun
Date

January 7, 2025

New research on four variants in the EPHA1 gene reveals how its genetic typos may contribute to risk of dementia

Upon inspecting the DNA sequences in patients suffering from Alzheimer’s disease, scientists have found evidence of an inconspicuous conspirator.

The EPHA1 gene contains the blueprint for the EPHA1 receptor protein, one of 14 such receptor proteins in the Eph receptor family. Relatively little is known about EPHA1 when compared to many of its siblings, making it difficult for researchers to ascertain why changes in its source code would contribute to such a debilitating disease.

Scientists at Sanford Burnham Prebys published results on December 18, 2024, in the Journal of Biological Chemistry, detailing the effects of four miniature mutations of just a single typo each in the sequence of nucleotides forming the EPHA1 gene.

These seemingly minor mutations are known as single nucleotide polymorphisms (SNPs), and they can lead to larger issues depending on where the typos fall in the sequence of a gene. The Sanford Burnham Prebys team focused on four missense mutations that are caused when SNPs result in different amino acids being used to build the EPHA1 receptor protein.

“Our data show that all four Alzheimer’s mutations we have characterized disrupt EPHA1 physiological signaling, and that the specific effects depend on the particular mutation,” said Elena Pasquale, PhD, professor in the Cancer Metabolism and Microenvironment Program at Sanford Burnham Prebys.

The team reported that the functional consequences of EPHA1 missense mutations identified in patients suffering from Alzheimer’s disease included misplacement of EPHA1 within cells, decreased protein stability and dysregulated signaling.

“To continue advancing knowledge on this topic, more work is needed to uncover the physiological role of the different EPHA1 signaling features and how their disruption may lead to neurodegeneration,” said Pasquale.


Additional authors on the study from Sanford Burnham Prebys include Mike Matsumoto and Sara Lombardi, PhD. Maricel Gomez-Soler, PhD, now works at Crinetics Pharmaceuticals in San Diego. Bernhard C. Lechtenberg, PhD, now works at the Walter and Eliza Hall Institute of Medical Research in Parkville, Australia.

Institute News

Science in Pictures

AuthorScott LaFee
Date

January 6, 2025

Beta-tubulin expression of a Drosophila (fruit fly) third instar larval brain, with attached eye imaginal discs.

Image courtesy of Christian Klambt and Imke Schmidt, University of Munster, Germany and Bioscapes.

Institute News

AI-driven cancer prediction tool makes NIH director’s highlights for 2024

AuthorScott LaFee
Date

January 3, 2025

On April 18, 2024, first author Sanju Sinha, PhD, an assistant professor in the Cancer Molecular Therapeutics Program at Sanford Burnham Prebys, and colleagues published details about a new artificial intelligence-powered tool called PERCEPTION (PERsonalized Single-Cell Expression-Based Planning for Treatments In ONcology).

PERCEPTION was proof-of-concept that AI could be used to predict a cancer’s treatment responses from bulk RNA. Sinha and colleagues built AI models for 44 drugs approved by the FDA and found that their tool “predicted the success of targeted treatments against cell lines with a high degree of accuracy.”

The paper was among six specifically highlighted by Monica Bertagnolli, MD, in her blog as director of the National Institutes of Health.

Institute News

Hudson Freeze finds life in hot water

AuthorScott LaFee
Date

January 2, 2025

Hudson Freeze, PhD, director and professor of the Human Genetics Program, has a starring cameo in Veritasium’s video profile of Kary Mullis, PhD, (1944-2019), an American biochemist who shared the 1993 Nobel Prize in Chemistry for his role in the invention of polymerase chain reaction (PCR), which fundamentally altered biochemistry, the study of DNA and helped lead to the new field of biotechnology.

Freeze, then a undergraduate student in the lab of Indiana University microbiologist Thomas D. Brock, PhD, (1926-2021), discovered a new species of bacteria able to live in 160 degree F. hot springs at Yellowstone National Park. Conventional wisdom at the time said no life could survive such temperatures.

After days of finding nothing in water samples, Freeze said he detected a “little something on the bottom” of a tube. “So I got a little pipette out, took a little drop, put it under a microscope.

“I still get goosebumps, man, I’ll tell you. I still get goosebumps. I looked at it and here were all of these worms, just crawling around. I thought, ‘My God, I’m the first person in the world to ever see this.’

“There was a graduate student in the lab and this graduate student says, ‘Well, I think we ought to call it ‘Hudsoniae Freeziensis.’

Instead, Brock and Freeze would name the novel bacterium Thermus aquaticus, learn how to cultivate it and publish their findings in 1969. Enzymes from T. aquaticus, which had evolved to function in extremely hot temperatures, would eventually provide a key tool  Mullis deployed to create PCR, which artificially amplifies minute DNA segments.

Institute News

Science in Pictures

AuthorScott LaFee
Date

December 30, 2024

What says happy holidays and Happy New Year better than a transverse section of rachis (stem) of bracken fern, created using differential interference contrast microscopy?

Image courtesy of David Maitland and Nikon Small World.

Institute News

Science in Pictures

AuthorScott LaFee
Date

December 23, 2024

This immunohistochemistry image, stained to visualize different stroma biomarkers in a mouse liver tumor,  colorfully captures the variegated heterogeneity of the tumor microenvironment.

Image courtesy of A.E. Nel, et al. National Cancer Institute.

Institute News

Science in Pictures

AuthorScott LaFee
Date

December 16, 2024

A 3D-structured illumination reveals a synaptonemal complex, a protein structure that forms between homologous chromosomes during cell division. It’s believed SCs function primarily as scaffolds to allow interacting chromatids to complete their crossover activities.

Image courtesy of Chung-Ju-Rachel Wang and Bioscapes.

Institute News

Sanford receives first Erkki Ruoslahti Award for Transformational Leadership

AuthorScott LaFee
Date

December 13, 2024

At a special event December 11, attended by trustees from Sanford Burnham Prebys and featuring brief talks by many of the Institute’s newest faculty, the inaugural Erkki Ruoslahti Award for Transformational Leadership was presented to T. Denny Sanford.

The new award honors recipients whose visionary leadership drives positive change, inspires groundbreaking solutions and contributes to the transformation of industries and society.

It is named after one of the institute’s earliest faculty and its president from 1989 to 2002. Ruoslahti made seminal contributions to the discovery of cell adhesion receptors known as integrins, helped developed a novel class of tumor-homing peptides and advanced the science of nanomedicine.

His past honors include elected membership to the U.S. National Academy of Sciences, National Academy of Medicine, American Academy of Arts and Sciences, and the European Molecular Biology Organization, the Japan Prize, Gairdner Foundation International Award, G.H.A. Clowes Award, Robert J. and Claire Pasarow Foundation Award and Jacobaeus International Prize.

In 2022, Ruoslahti was announced as one of three winners of the Albert Lasker Basic Medical Research Award, sometimes called “America’s Nobel.”

Sanford is, of course, one of the institute’s three namesakes, a distinguished businessman and philanthropist who has long supported its work and vision.

“Denny Sanford has been a friend, supporter and mentor for many, many years. He believes in the importance and value of both basic and translational science, of helping patients and the world become better and healthier,” said Brenner.

“His past, present and future support of Sanford Burnham Prebys is critical to our vision and mission. No one has done more. This award is a heart-felt, tangible symbol of our gratitude.”

Watch Award Presentation
Institute News

Science in Pictures

AuthorScott LaFee
Date

December 9, 2024

This image of the hippocampus in a rat brain was taken using an ultra-widefield high-speed multiphoton laser microscope. Tissue was stained to reveal the organization of glial cells (cyan), neurofilaments (green) and DNA (yellow).

Image courtesy of Thomas Deerinck, NCMIR and NIH.