genetic engineering Archives - Sanford Burnham Prebys
Institute News

Jamey Marth interviewed by The Scientist

AuthorGreg Calhoun
Date

October 31, 2024

The Sanford Burnham Prebys scientist discussed the Cre-loxP recombination system, which continues to be a mainstay genetic engineering technology.

“Techniques come and go with new technology, it’s just like night and day.” said Jamey Marth, PhD, professor and director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys during his interview with The Scientist regarding his lab’s contributions to a genetic engineering technique that has stood the test of time.

“So, when you have a technique that’s lasted 30 years with no replacement technology, I think that’s kind of remarkable.”

Marth was interviewed about the Cre-loxP recombination system, which acts as a molecular genetic editor for controlling mutations in the genome. It was initially investigated by Drs. Nat Sternberg and Brian Sauer in the 1980s in tests to manipulate the genes of yeast and mammalian cells.

Marth wanted to use the technique for conditional mutagenesis in animal studies that would enable temporal and cell-type specific genetic models to better investigate biological systems and more effectively model human diseases. He and his team advanced the Cre-loxP system for use in laboratory mice and demonstrated the ability to efficiently delete DNA sequences in specific T cells in 1992.

The Cre-loxP recombination system continues to be a mainstay technology today and some scientists are exploring ways to combine it with the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated nuclease, Cas9, to gain the advantages of both genetic engineering techniques.

Institute News

Genes and proteins go hand-in-hand

AuthorBill Stallcup, PhD
Date

July 14, 2017

Thanks to huge improvements in DNA sequencing technology, scientists have identified almost all the genes present in humans. Despite this achievement, there are still thousands of genes whose functions remain a mystery. Since genes are basically blueprints for making the proteins needed to run our cellular machinery, connecting genes with the specific functions of their encoded proteins is a critical next step in using genomic information to solve health-related problems.

Bridging the gap between gene sequence and protein function is the topic of a study published in the Journal of Biological Chemistry by Yu Yamaguchi, MD, PhD, professor at SBP. According to Yamaguchi, “There has been a long-standing mystery concerning the processing of hyaluronic acid (HA), a large sponge-like molecule required to maintain proper spacing between neighboring cells. We had already learned a lot about how cells make HA, but the other equally important side of the equation is how HA is broken down, which is needed to prevent HA build-up that can cause tissue fibrosis.”

The Yamaguchi lab knew that HA degradation must be accomplished by enzymes that cut HA into smaller pieces for further processing. “However, none of the known HA-cutting enzymes had the ability to cut the very large HA that exists outside the cell”, explains postdoctoral fellow Hayato Yamamoto, MD, PhD, first author on the study. “We decided to search gene sequence libraries to identify other proteins that were not previously suspected to cut HA, but which were structurally similar to known HA cutters.”

Their search turned up transmembrane protein 2 (TMEM2), whose structure predicted that it would exist on the cell surface and would also be able to cut HA. “My job was then to determine whether or not this protein could live up to our predictions,” recalls Yamaguchi. “We were able to show experimentally that the protein really did exist on the cell surface and was able to cut large HA molecules into smaller fragments for further processing inside the cell.”

Read the paper here.

Institute News

CRISPR: a new era in gene editing

Authorjmoore
Date

March 29, 2016

If you’ve been paying attention to science news, you’ve probably heard a lot about genome editing and the technology that’s made it so widely used, CRISPR (pronounced “crisper”). Most controversially, a team in China edited the genomes of human embryos — a landmark event that raised concerns of a slippery slope towards unethical uses. Nonetheless, few doubt that the technology will revolutionize research and treatment of genetic disease. Continue reading “CRISPR: a new era in gene editing”