Rac2 Boosts Cancer Therapy: 

In a remarkable breakthrough, researchers from UC Santa Barbara’s Molecular, Cellular, and Developmental Biology department have cracked a 25-year-old cellular mystery, connecting the gene Rac2 to a rare human immunodeficiency disorder. This groundbreaking research, led by distinguished professors Denise Montell and Meghan Morrissey, not only sheds light on the intricate workings of cell biology but also presents promising avenues for advancing cancer therapies.The focal point of the study is the Rac2 gene, a vital component in cell biology. Rac proteins, including Rac2, play a pivotal role in constructing a cell’s cytoskeleton, the structural framework crucial for maintaining cell shape. Montell’s team began their research by studying fruit flies, where hyperactive Rac proteins were found to induce cannibalistic behavior in cells, leading to the destruction of entire tissues. The research took an unexpected turn when the researchers learned of a study involving patients with a Rac2 mutation that resulted in a mysterious immunodeficiency disorder.

By connecting the dots between fruit fly observations and the patient study, the team discovered that macrophages with active Rac2 were consuming T cells, providing a crucial clue to the immunodeficiency mystery. The implications of this discovery reach beyond immunodeficiency, extending into the realm of cancer treatment. Collaborating with Morrissey, an assistant professor of Molecular, Cellular, and Developmental Biology at UCSB, the team explored the potential of enhancing a novel cancer treatment called CAR-M. By integrating activated Rac2 into the mix, researchers observed a significant boost in macrophages’ ability to consume cancer cells, laying the foundation for a groundbreaking cancer therapy.The proposed cancer treatment, named RaceCAR-M, involves finely manipulating macrophages to selectively target and consume cancerous cells. The team has filed a provisional patent for this innovative technique and is actively seeking collaborations with biotech companies for further development. Denise Montell expressed her enthusiasm. “This is my favorite paper so far. We had this 25-year-old cold case in fruit flies, and we solved it,” Montell said. “And that helped us solve the mystery of an unexplained human immunodeficiency. And then we harnessed that knowledge to enhance potential cancer immunotherapy.” As researchers continue to delve into the molecular intricacies, the future holds promising developments at the intersection of basic cell biology and therapeutic innovation.

Sea Otters Restore Ecosystems:

Sea otters are playing a vital role in the ecological restoration of Central California’s wetlands, particularly in the Elkhorn Slough, according to a pioneering study led by researchers at UCSB. Published in Nature, the research highlights the remarkable impact of sea otter recolonization on the region’s landscape.The study reveals a notable 69% reduction in the erosion of creek banks after the sea otter population fully recovered, defying expectations given factors such as rising sea levels and stronger tidal currents. Marsh and streamside vegetation have also rebounded, offering increased resilience against flooding and wave surges. The key driver behind this rejuvenation is the sea otters’ voracious appetite for herbivorous marsh crabs, as explained by co-author Kathryn Beheshti, an assistant researcher at UCSB’s Marine Science Institute.

Lead author Brent Hughes, an associate professor of biology at Sonoma State University, emphasized the significance of the sea otters’ role. “Our study underscores the far-reaching benefits that can cascade through an ecosystem when a top predator is reintroduced,” Hughes said. The sea otters’ return to Elkhorn Slough in the mid-1980s and their subsequent expansion into salt marshes have led to the stabilization of salt marshes and creek banks, countering decades of erosion caused by an overpopulation of crabs.

Senior author Brian Silliman, a distinguished professor of marine conservation biology at Duke University, posed an intriguing question: “In how many other ecosystems worldwide could the reintroduction of a former top predator yield similar benefits?”The study’s insights challenge the traditional understanding of coastal geomorphology, highlighting the crucial role predators play in shaping tidal creeks. The research, combining field experiments, modeling and before-and-after measurements, provides a compelling case for the far-reaching impacts of reintroducing top predators into ecosystems. The sea otters’ role in stabilizing wetlands offers an effective and cost-efficient tool for conservation efforts, allowing natural restoration to occur without extensive human intervention. As the study opens new avenues of exploration, researchers are initiating further projects to understand and enhance the sea otters’ impact on ecosystem restoration.

Comet Research in Wakulla Springs:

In the heart of Wakulla Springs, one of the world’s largest and deepest freshwater springs, a team led by UCSB Professor Emeritus James Kennett has unearthed a cosmic time capsule hidden in the aftermath of a fragmented comet’s collision with Earth’s atmosphere some 13,000 years ago. While the celestial event is already linked to global repercussions such as burning, impact winter and megafauna extinction, it has now emerged as an invaluable tool for dating stone artifacts. Published in the prestigious Nature journal, the study introduces a novel approach centered around the Younger Dryas Boundary (YDB) layer, formed during the cosmic impact. This layer, distinguished by materials forged at temperatures surpassing 2,000 degrees Celsius, is globally distributed, spanning the Americas, Western Europe and the Middle East. Wakulla Springs in northern Florida, a site with a rich history of human habitation, posed unique challenges due to its sandy soils and continuous occupation, complicating conventional dating methods. “The Florida sites have a certain archaeological sequence of stone tools with only generally known cultural ages,” Kennett elaborated. “The idea was to try and see if we could use the 12,800-year-old YDB to more clearly define the cultural ages and their sequence represented in these sites.”

Addressing these challenges, the researchers employed an approach that integrated platinum geochemistry, granulometry, optically stimulated luminescence (OSL) dating and dating of stone artifacts. Despite the limitations of OSL dating, the team identified iron-rich microspherules and high platinum concentrations around a meter below the surface at each site – distinctive markers of the YDB layer. “The layer containing platinum and microspherules is well-dated to 12,000 years ago at many other sites, therefore, it provides a very useful age level for correlation and dating between the sequences at Wakulla,” Kennett said. This breakthrough not only ensures precise dating of archaeological sequences but also facilitates correlation across multiple sites, offering a better understanding of the paleohistory of the area. By amalgamating OSL data, the YDB layer and artifact presence, the researchers successfully established relative ages of stone tools pre- and post-YDB formation. “A lot of archaeological sequences are difficult to date with accuracy, and hence the identification of the YDB layer presents a significant advance,” Kennett said. This cosmic time capsule not only sheds light on ancient events but also pioneers a new frontier in archaeological methodology, unraveling the intricate tapestry of human history through meticulous dating and correlation techniques. 

A version of this article appeared on pg. 8 of the Feb. 29, 2024 print edition of the Daily Nexus.