August 3, 2007

Summer Assignment: Genetically Engineer a New Cell

Just a few weeks ago, they were finishing high school. Today, they're trying to reprogram the "molecular bar code" that distinguishes one part in a cell from another. Six pre-college students and one undergraduate are working with UCSF graduate student and postdoc mentors to fashion a new kind of organelle inside a living cell. The young graduates from Lincoln High School in San Francisco came up with the ambitious project themselves, and by the end of the summer they hope to travel to Cambridge, Massachusetts to enter their living creation in the International Genetically Engineered Machine (iGEM) competition sponsored by MIT. This competition draws talent from all over the world. "Most teams in this competition are college students," says Wendell Lim, PhD, UCSF professor of cellular and molecular pharmacology and one of the budding scientists' hosts. "But since we don't have any undergraduates at UCSF, we decided to put together a team with some of the top high school students from the San Francisco public schools." So far the team has been impressive. "After just five weeks in our lab, these young people have jumped to the level of graduate students," Lim claims.

Summer Lab Program Supported by SEP and QB3

The students' participation was conceived with help from UCSF's SEP program - the Science and Health Education Partnership between UCSF and the San Francisco Unified School District, designed to help boost student science literacy in the city. The SEP High School Summer Internship program targets students for whom the program will make a critical difference in their lives. The majority of these students are the first in their families to attend college; over 70 percent of the students intend to go onto or have begun graduate school and earn either a PhD, MD, Pharm D, or DDS degree. The UCSF summer lab experience also is supported in part by the NSF synthetic biology and NIH nanomedicine research centers at QB3, directed by Lim. UCSF postdoctoral fellow Sergio Peisajovich, PhD, is scientific director of the program. Faculty members Hana El-Samad, PhD, Tanja Kortemme, PhD, and Chris Voigt, PhD, are also participating in the program. The UCSF teaching assistants who mentored the young students include Lim lab graduate students Angela Won and Reid Williams; David Pincus, a graduate student in the lab of Peter Walter, PhD; Ryan Ritterson, a graduate student from Kortemme's lab; and Lim lab postdocs Noah Helman and Andrew Horwitz.

Lim and Students Explain the Theory Behind the Project

Most cells, from yeast to humans, have many kinds of compartments or organelles, each isolated from the rest of cell, and each charged with a different task, Lim explains. Energy for the cell is generated in the mitochondria, for example, while lysosomes act as a kind of garbage disposal, degrading unneeded cell material.

Clockwise from left: Eric Meltzer, Palo Alto HS; Sergio Peisajovich, postdoctoral fellow, Lim Lab and scientific director of iGEM team; Eric Chou, Lincoln HS; Michael Chen, UC Berkeley; Alex Ng, Lincoln HS; Jimmy Huang, Lincoln HS. Center: Lauren Jann, Lincoln HS. Missing from photo: Robert Ovadia, Lincoln HS; Nili Sommovilla, UCSF iGEM team coordinator.

"Different organelles in a cell have are marked with different molecular codes. In many cases this is encoded by the number and position of phosphate groups on the outside of the organelle," explains Jimmy Huang, one of the Lincoln High grads in the UCSF summer lab. "The phosphates distinguish one compartment from another," adds Lauren Jann, a team member who just graduated from Lincoln High. Compartmentalization is critical, Lim explains, since many cell processes would harm the rest of the cell if they weren't isolated in an organelle. The lysosome that degrades unneeded proteins could destroy vital cell parts. The chemical process that creates energy-rich ATP in the mitochondria compartment involves toxic intermediate steps which also must be sequestered. "If we wanted a new organelle to become, let's say, a drug- or biofuel-producing site inside a cell, the first step would be to create the new organelle by marking it with its own phosphate bar code. That's what the team is trying to do," says undergraduate student Michael Chen.

Program Participants Impress UCSF Graduate Students, Postdocs and Faculty

For the first few weeks, the students were cautious and asked lots of questions, says Ritterson. "But in four weeks, they became very independent," he adds. Pincus confirms, "I was impressed by how quickly they catch on. Plus they understood a lot of principles going in."

The team is labeling the cell's organelles with fluorescent proteins in order to observe the size, localization, and lifetime of the compartments. By targeting the fluorescent probes to the molecular signatures that uniquely identify each organelle, the group can distinguish between different cellular components. Similar imaging experiments have already been demonstrated, as in the image below in which budding vesicles are labeled in green and internalized vesicles appear in red.Image courtesy of Mark von Zastrow lab, UCSF.

Many of these principles, along with the students, came from an unusual two-year high school biotechnology curriculum led by Lincoln High teachers Julie Reis and George Cachianes. Reis and Cachianes developed their course with support from the Genentech Foundation. Lim thinks the young team climbing the steep learning curve in his lab this summer has a good chance in the international MIT competition come fall. Even though their bioengineered creation will be up against college student projects, "these kids are great," he says. "If they follow the trajectory they are on, they could easily become biotech leaders."

Summer Lab Program Supported by SEP and QB3

Lim and Students Explain the Theory Behind the Project

Program Participants Impress UCSF Graduate Students, Postdocs and Faculty

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