Its important to be able to control the timing and spacing of the gene knockouts so the researchers can look at the same mice over time, and test for different situations.

VHL helps control cells response to different oxygen levels, especially low levels. Our current data indicates that VHL gene deletion accelerates the production of red blood cells and helps create blood vessels in the bone and bone marrow, Spencer said. This, in turn, impacts how B-cells develop.

The researchers will be able to peer inside the bone marrow and see how the microenvironment has changed when VHL is deleted in the mesenchymal cells and pre-osteoblasts. Several diseases are linked to the marrow microenvironment, so the research has the potential to inform the work of many other research teams as could the development of the new mouse model. Manilay said many researchers have tried to build models with the same specifications she and Spencer need, but those models have not worked.

Were trying something different, so this could really help researchers all over the world if it works, she said. This is high-risk, high-reward research. The risk is this could completely fail, but even then, wed be able to provide information to other researchers.

This $400,000, two-year R21 grant builds on an NIH R15 award the team received last year to examine the effects of the VHL gene defect that makes the bones grow extremely dense, with little room for marrow. Because marrow is where both immune system and blood cells develop, less marrow than normal could have a wide range of negative consequences, and the team wanted to know whether immune cells were responding to altered oxygen conditions, which are also a hallmark of the defect. B-cells can sense when they are in low-oxygen conditions, Spencer said, and they can turn on genes to help them adapt.

Spencer, whose research focuses on biomedical imaging, became the first scientist to capture an image of native adult hematopoietic stem cells (HSC) within the bone marrow of a living organism. Manilay is interested in the relationship between bone and bone marrows HSCs on immune cells fates.

Spencer, with the Department of Bioengineering in the School of Engineering, and Manilay, with the Department of Molecular and Cell Biology in the School of Natural Sciences, are both members of the Health Sciences Research Institute.They worked on the foundation of this research for more than a year before the first grant started. Manilays lab had gathered preliminary data, including some work done by graduate student Betsabel Chicana, who recently won an NIH fellowship for her immunology work. The graduate students collaborated throughout, analyzing data and cross-training in each others disciplines.

Now that weve been doing this for more than a year, Im really seeing the benefits among my students, Spencer said. Exposing them to other research methods and other ways to ask questions and design experiments gives them a broader training, which will benefit their futures as researchers.

View post:
Collaboration Furthers Understanding of Immune Cell Development | Newsroom - UC Merced University News

Comments are closed.