Insights & Outcomes: A multi-tasking protein and applied math prowess

Insights & Outcomes welcomes the start of summer break with an honor for a Yale applied mathematician, a protein that multitasks, new insights into some colorful sediments, and a new way to study a key area of the human brain.

As always, you can find more science and medicine research news on Yale News’ Science & Technology and Health & Medicine pages.

Bands of gold — and orange, yellow, and brown

A project that began as a collaboration among researchers in Yale’s Department of Earth & Planetary Sciences may cause scientists to rethink Earth’s banded iron formations — colorful layers of sedimentary rock made of iron oxides.

In a study in Nature Geoscience, Jay Ague, the Henry Barnard Davis Memorial Professor of Earth & Planetary Sciences, and former Yale researchers Duncan Keller (now a faculty member at Rice University), Santiago Tassara (now at Bernardo O’Higgins University in Chile), and Leslie Robbins (now with the University of Regina in Canada) have linked banded iron formations with some of the planet’s most fundamental geophysical processes, from volcanism and plate tectonics to the development of photosynthetic life.

The authors posit that heavy, banded iron formations — formed in ancient oceans — plunged into Earth’s mantle layer over time and sank deep enough to settle near the top of the Earth’s core. This process may have aided in the formation of mantle plumes — narrow belts of heated rock at the boundary of the mantle and core — which can lead to powerful volcanic activity at Earth’s surface.

“If what’s happening in the early oceans after microorganisms chemically change surficial environments ultimately creates an enormous outpouring of lava somewhere else on Earth 250 million years later, that’s much greater length scale processes talking to each other that were previously thought of as unrelated,” said Keller, who is first author of the study.

Rajdeep Dasgupta, a professor of Earth Systems Science at Rice, and Cin-Ty Lee, a professor of geology, Earth, environmental, and planetary sciences at Rice, are co-authors of the study.

Making sense of a multi-tasking protein

Our bodies reproduce trillions of new cells in order to grow and develop. But when our DNA divides unevenly, the resulting stress in our cells can lead to diseases such as cancer. The separation of DNA into new cells — a process called mitosis — is carefully controlled and protected by certain proteins that scientists have yet to fully understand.

New research from the Yale Cancer Biology Institute (YCBI), located on Yale’s West Campus, has uncovered a new and important role for a protein previously thought to perform just one task — to protect cells only by responding to DNA damage and cell stress.

Yale scientists found that the protein — called ATR — has another job: protector of genome stability. Their findings, published in the journal Cell Reports, offer a new perspective on ATR’s function and the importance of DNA composition for cellular processes.

“We’re trying to understand the mechanisms that protect against uneven cell division,” said Lilian Kabeche, assistant professor in the Department of Molecular Biophysics and Biochemistry, a member of the YCBI, and senior author of the study. “When we identify all the ways a protein works, we can better predict how drugs targeting that protein will affect patients.”

Currently, ATR is targeted by inhibitor therapies in cancer treatment. But based on these new findings, the scientists hope to explore new therapeutic targets that also work to protect healthy cells, for example to prevent the side effects of chemotherapy.

Graduate student Isabelle Trier, who was first author of the study, led lab experiments for the study. Additional authors from the Kabeche Lab were Elizabeth Black and Yoon Ki Joo. The work is supported by a Pershing Square Sohn Award.

Wettlaufer selected as 2023 SIAM Fellow

The Society for Industrial and Applied Mathematics (SIAM) recently selected Yale’s John S. Wettlaufer as one of its 2023 fellows.

SIAM is an international community of more than 14,000 members, including applied and computational mathematicians, computer scientists, and engineers. New fellows are honored for their role as leading thinkers and ambassadors of applied mathematics and computational science.

Wettlaufer, the A.M. Bateman Professor of Geophysics, Mathematics, and Physics in Yale’s Faculty of Arts and Sciences, was recognized for his fundamental contributions to the modeling of interfacial problems, the study of ice, geophysics, and climate dynamics. Wettlaufer is one of 26 new SIAM fellows.

“It is a privilege to have had my work recognized, and I hope that the diversity of applied math at Yale, from analysis to computation and everything between, will continue to be recognized both within and outside the university,” Wettlaufer said. “Indeed, as a longtime dean of undergraduate studies for applied mathematics, I have the privilege of guiding students through the myriad of potentialities that a quantitative approach allows them to explore, and I look forward to seeing some of them involved in the SIAM community in the future.”

Wettlaufer joins Yale faculty members Vladimir Rokhlin, Mitchell Smooke, and the late Stanley Eisenstat as SIAM Fellows.

In the thick of the thalamus

The creation of brain organoids — three-dimensional tissue cultures, grown from stem cells, that stimulate the structure of different organs — has greatly enhanced the ability of scientists to study human brain development and diseases. However, the challenge of recreating highly specialized areas such as the thalamus — which contains 60 distinct nuclei that each exert control over the flow of sensory information to different brain regions — has so far proved difficult.

In a new study in the journal Cell Stem Cell, researchers in the lab of In-Hyun Park, associate professor of genetics at Yale, used human stem cells to create brain organoids with a key portion of the thalamus called the thalamic reticular nucleus (TRN) that fine-tunes sensory information before it reaches the cortex.

In developing their method for creating the thalamic organoids, the researchers discovered that several transcriptionally distinct subpopulations in the TRN cell cluster share marker expressions also observed in the TRN of mice, for example.

Abnormalities in TRN development and function have been associated with many neurodevelopmental diseases and sleep disorders. This specialized organoid will help scientists understand the development of disorders as varied as schizophrenia, autism, and ADHD, Park said.

Ferdi Ridvan Kiral and Bilal Cakir, both from Yale School of Medicine, are co-first authors of the new study.

Research Redux:

Arrays of magnetic energy shown to flex, wiggle, and reconnect

‘Deletions’ from the human genome may be what made us human

A ‘slingshot scenario’: On the trail of a runaway supermassive black hole

Study identifies compounds that may improve treatment of opioid addiction

Researchers double a qubit’s life, proving key theory of quantum physics