While Griffith and her counterparts on the engineering faculty explore various innovative ideas, their biology counterparts are navigating new terrain, too.
Over a decade ago, Nancy Hopkins, professor of biology and a cancer center member, started doing studies of a relatively uncommon lab model of disease: the zebrafish. This creature, which is roughly an inch long and looks like something you might turn up in a home aquarium, has many advantages as a disease model. Among them is the fact it’s all but transparent in its embryonic state, so you can easily track major changes in its body. It also has many genes in common with mammals, including humans.
Hopkins has engineered a series of gene mutations in the fish so she can study the health and developmental impacts of those changes. A few years ago, she and Jacqueline Lees, associate head of the MIT cancer center, were screening that stable of mutants for cancer. What they discovered, says Lees, was “a huge surprise.”
It turned out that if certain genes involved in the cells’ machinery for making proteins were affected by a specific type of damage, cancer resulted. So why the surprise? Because some of the genes involved were, in effect, eliminated. Scientific dogma held that the only way those particular types of genes could cause cancer was if they were over-active, says Lees, also a professor of biology.
The finding was so counterintuitive the pair had trouble publishing their findings. “There was a lot of resistance to our paper,” says Lees. “People thought that the phenomenon should work the other way around.”
The results were finally published this past summer. Meanwhile, Hopkins and Lees have not only been looking for other types of cancer-linked gene defects but also probing for connections between those fish tumors and human disease.
They think they’ve found one. There’s a rare form of congenital anemia that involves human genes similar to the genes targeted by the MIT researchers. About a quarter of the people with that ailment develop a tumor of the nervous system.
Probing the link between the genetic mutations the pair found in fish and that type of human tumor may take a while. “When a syndrome affects only a small number of people,” says Lees, “it’s hard to tell whether these individuals get a particular type of cancer more frequently than the general population.”
But however that study turns out, the more intriguing question is whether the genes under scrutiny — which code for proteins, called ribosoal proteins, that are intimately involved in our cells’ manufacturing centers — may have a role in a range of human tumors. “There are numerous malignancies whose genetic origins are unclear,” notes Lees, “and we’d like to find out if some of these are linked to genes that code for ribosomal proteins.”