Maxi D’Angelo grew up in Neuquén, Argentina. During his graduate studies in molecular biology at the University of Buenos Aires, he and Marcela Raices, a graduate student in the lab next door, fell in love. They married and came to the San Diego area for postdoctoral fellowships, in different labs, because the United States has the most resources, “by far,” for research, he said.

Leaving Argentina for a postdoctoral fellowship is “necessary training,” Maxi told me. It broadens connections and allows scientists to attend more international scientific meetings, because many are held in the United States and because U.S. labs have the resources to send fellows to meetings around the world. Also, moving to the United States is a good way to improve English, a refrain I’ve heard before from non-American scientists.

Maxi’s research centers on the cell’s nucleus, where DNA is stored and copied, where RNA is transcribed and then exported outside the nucleus to specify protein production. The nucleus is surrounded by two membranes that act as a barrier, separating it from the rest of the cell’s interior. Many molecules need to be transported into or out of the nucleus, so the nuclear membranes have pores, tunnels that regulate access to the nucleus. The only nuclear membrane pore that spans both membranes, linking the interior of the nucleus directly to the rest of the cell, is the creatively named nuclear pore complex, composed of many copies of 30 different proteins.

At the core of this large complex is a scaffold that surrounds the actual channel. When cells divide, the entire nuclear core complex disassembles and reassembles in the daughter cells. But when the cell is not dividing, only the proteins in the outer part of the complex, not the scaffold, are replaced – part of routine maintenance. So how is the structural integrity of the nuclear pore scaffold maintained in cells, like neurons in the adult brain, that no longer divide?

It isn’t. As Maxi discovered while working in Martin Hetzer’s lab, the proteins that make up the scaffold are not produced or replaced in nondividing cells. To make matters worse, as cells age their scaffolds degrade, and this compromises the nucleus, allowing proteins that are normally blocked to enter the nucleus. Maxi performed these experiments in the roundworm C. elegans, thanks to his wife, who uses the worm in her research. He got similar results using cells from rat brains, proving again that the core machinery in cells is similar throughout the animal kingdom.

Maxi said he would love to return to Argentina as an assistant professor and lead a lab (this discovery makes him a competitive candidate at top universities around the world), but the lack of resources and physical space in which to work are barriers. In Argentina there are good scientists doing good work, but the low budget makes it “difficult to do the latest science,” work. For now, Maxi plans to apply for faculty positions at universities in the United States and Europe.

When Maxi and Marcela came to the United States in 2003, Maxi began working in Larry Gerace’s laboratory at the Scripps Research Institute. It wasn’t a good fit, so a year later he moved across town to work with Hetzer at the Salk Institute, and once again found himself next door to Marcela. “We’re destined to be next to each other in the lab.”

Like two proteins in the nuclear pore complex scaffold.

Source: “Age-Dependent Deterioration of Nuclear Pore Complexes Causes a Loss of Nuclear Integrity in Postmitotic Cells” by Maximiliano A. D’Angelo, Marcela Raices, Siler H. Panowski, and Martin W. Hetzer, published in the January 23 issue of Cell.