Cell biology research using bomb-pulse dating

Overview

LLNL scientists use a radiocarbon dating technique to analyze isotopic signatures in biological material and measure cellular and molecular turnover with high precision. This process leverages the Lab’s bioAMS capabilities to measure the ratio of carbon-14 to other carbon isotopes in a biological sample—including cells, tissue, and proteins—enabling scientists to determine a material’s age.

This radiocarbon dating technique, also known as bomb-pulse biology, takes advantage of the sharp increase and subsequent slow decrease of atmospheric carbon-14 concentrations that occurred due to atmospheric testing of nuclear weapons from 1955 to 1963. During that timeframe, the level of carbon-14 in the atmosphere doubled across the globe. Since above-ground testing was banned in 1963, atmospheric carbon-14 levels have been dropping due to diffusion, as carbon dioxide is incorporated into plants by photosynthesis and mixed with marine and terrestrial carbon reservoirs.

By eating plants, and animals that feed on plants, the concentration of carbon-14 in the human body closely parallels atmospheric concentrations. Thus, the rapid rise, sharp peak, and exponential decline of atmospheric carbon provides a molecular time stamp, enabling scientists to date biobased material more precisely.

Long-term immunity provided by memory T cells

Illustration depicting the immune system. — LLNL scientists are studying memory T cells to better understand how they provide long-term protective immunity for humans as they age.

Researchers from LLNL and their collaborators are studying the aging and turnover process of memory T cells in human tissues, providing insight regarding how these antigen-specific white blood cells, which remain in the body after an infection is cleared, provide long-term protective immunity. Memory T cells are generated in response to infections and vaccines, and they provide protection when a person is exposed to the same pathogen in the future by generating an effective immune response. To better understand whether memory T cells become less effective as they age, researchers studied T cell turnover in the lymphatic system, mucous membranes, and blood.

They used LLNL’s bioAMS capabilities to determine the age of human T cells in blood and tissue samples provided by organ donors. Researchers found that T cells age at different rates, based on their location in the human body and the type of tissue involved (e.g., T cells found in the spleen had a much longer lifespan than T cells found in blood, lymph nodes, lungs, and intestines). In addition, the tissue environment effects functional changes that T cells undergo as they age. These findings provide insight regarding how to develop immune modulation strategies for humans as they age, including better vaccines and therapeutics.

Key collaborator: Columbia University

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Identifying risk factors for brain aneurysm ruptures

Illustration of the brain. — LLNL scientists are studying risk factors for cerebral aneurysms.

Researchers from LLNL and their collaborators are exploring factors that affect the growth and rupture of cerebral aneurysms in humans, hoping to better understand factors that impact the structural stability of aneurysms. The overall aim of their research is to identify risk factors that can be modified to help prevent ruptures.

The research team is measuring turnover rates of collagen in brain aneurysms, and then comparing that information with patient data regarding individuals who have more stable, unruptured aneurysms that do not experience periods of growth and instability. They use LLNL’s radiocarbon dating capabilities to determine the age of collagen in aneurysms, providing insight regarding the age of the aneurysm and its long-term stability. By comparing these findings with patient data regarding specific risk factors (e.g., smoking and hypertension; the size and site of the aneurysm), they can pinpoint risk factors that can be modified.

Key collaborator: University of Heidelberg, Mannheim, Germany

What’s next: The team plans to expand this research and explore other vascular structures, such as arteries. They will use radiocarbon dating techniques to determine the progression and stability of arteriovenous malformations (AVMs). Collaborators at the University of Heidelberg will continue to be involved as they explore AVMs, and the team will also include researchers at the University of California, San Francisco.