NOV 20, 2018 12:58 PM PST

Mutations Mutations Which Ones Do We Want?

WRITTEN BY: Nicholas Breehl

Often we find ourselves avoiding mutation when it comes to our DNA. We avoid the sun’s UV radiation, smoking, asbestos and other carcinogenic factors which can cause our DNA to mutate. Too many mutations of this sort can lead to cancer. However, when the mutation is performed intentionally in a safe manner, it lends us the advantage of determining the specific function of our genetic makeup.

A team of researchers at the University of California San Francisco have made use of a new tool known as SLICE that utilizes CRISPR gene editing techniques to induce mutation. SLICE enables the rapid assessment of the function of every gene in primary immune cells. Primary immune cells are the cells that come directly from the patient. The experiments are described in the November 15 issue of Cell.

"SLICE allows us to perform genome-wide screens in which we mutate every gene in the genome to see which genes have the biggest effect on the cellular behavior we're interested in," explains Alex Marson, MD, Ph.D., associate professor of microbiology and immunology at UCSF and co-senior author of the new study. "We change one gene at a time in each cell and see which change causes the cell to do what we want it to do. SLICE is the discovery engine that will point us towards pathways that we can reprogram to generate the most effective next-generation cell therapies."

The research team utilizes SLICE to figure out which of the immune cell's genes are responsible for the increase in their cancer-killing immune activity. The team focused on mutations of the T cells, cells responsible for the attack and elimination of foreign material.

Various immunotherapies exist that employ T cells to find and kill cancer. Though the T cells are effective, it is observed that they do not always perform as expected. Once SLICE identified the genes that could dampen the effectiveness of the T cells, they deleted them and witnessed a markedly improved cancer-killing capacity. This work proved that scientists could use SLICE to identify genes that make T cells proliferate.

Another challenge the scientists acknowledge is that of the tumor microenvironment. In the tumor microenvironment, the T cells can become suppressed. The team hoped the SLICE tool would aid in overcoming the suppression.

"SLICE functions as a flexible platform that allows scientists to model the interaction between immune cells and the tumor microenvironment. We've shown that SLICE can help researchers identify genes that allow immune cells to escape the immunosuppressive forces they encounter in these microenvironments," said Alan Ashworth, PhD, the E. Dixon Heise Distinguished Professor in Oncology at UCSF, president of the UCSF Helen Diller Family Comprehensive Cancer Center, and co-senior author of the new study.

The team hopes that the SLICE tool may one day help improve upon personalized immune cells to battle cancer. "Given the flexibility of this approach," Marson said, "SLICE may one day help scientists to create personalized immune cells with novel disease-fighting properties."

Watch this video to learn more details about a tumor microenvironment.

Sources: Science Daily, UCSF, YouTube

About the Author
Master's (MA/MS/Other)
You May Also Like
NOV 25, 2022
Clinical & Molecular DX
How a Multivalent Flu Vaccine Could Fight Against Future Pandemics
How a Multivalent Flu Vaccine Could Fight Against Future Pandemics
Scientists at the University of Pennsylvania have developed an experimental mRNA vaccine that protects against all known ...
NOV 28, 2022
Microbiology
A Vaccine to Prevent Urinary Tract Infections is in Development
A Vaccine to Prevent Urinary Tract Infections is in Development
New research has shown that a vaccine for the bacteria commonly associated with urinary tract infections works in animal ...
DEC 06, 2022
Immunology
Dishwasher Rinse Chemicals Seem to Harm the Protective Gut Lining
Dishwasher Rinse Chemicals Seem to Harm the Protective Gut Lining
Commercial dishwashers are used in many places, including restaurants, schools, and military barracks. The rinse agents ...
DEC 14, 2022
Clinical & Molecular DX
Scientists Identify Compound that Could Broadly Fight Coronavirus Infections
Scientists Identify Compound that Could Broadly Fight Coronavirus Infections
Researchers at the University of British Columbia have identified a compound that shows promise in targeting a wide rang ...
DEC 28, 2022
Immunology
Shedding LIGHT on the Mechanisms Underlying Severe Asthma
Shedding LIGHT on the Mechanisms Underlying Severe Asthma
Scientists have discovered that an inflammatory cytokine known as LIGHT is a major factor in the deadly airway damage th ...
JAN 24, 2023
Immunology
Remove Dead Cells for Increased Accuracy
Remove Dead Cells for Increased Accuracy
Even viability dyes need controls. Don’t have time to “kill” a control for this? Don’t worry- we ...
Loading Comments...