Posted on Jan 3, 2014
If you asked most undergraduates whether they would be interested in factory work, you’d probably get some puzzled looks. But what if the “factory” was E. coli bacteria, and the “work” involved creating entire libraries of enzymes that might help defeat antibiotic resistance or cancer?
Undergraduates in Dr. Gavin Williams’ lab get to do just that, with hands-on, real research experience that starts as soon as they walk through the door.
Williams is interested in drug development. Specifically, he’s interested in using E. coli as a factory to produce molecules that can be used as anti-cancer, anti-microbial and anti-viral drugs. What does that mean? Think about penicillin – it comes from a natural product (mold) that has antibacterial properties.
Nature makes these complex molecules by putting different types of enzymes into assembly lines, each of which can construct a molecule that may have a desirable quality, like the ability to stop bacterial growth or kill cancerous cells. In traditional drug development, scientists try to mimic natural processes by using chemicals. The problem is that these chemical processes are wasteful: in some cases it can take almost a ton of starting materials to produce one gram of the compound needed.
“I came to NC State because I knew I wanted to do research” — Matthew Draelos, senior chemistry and biochemistry major.
Williams and other chemists have found a shortcut. They go straight to the source – DNA – and pull out the particular genes that encode the enzymes they’re interested in. They can then manipulate those enzymes so that they only bind to other specific proteins. It’s like assembling a LEGO sculpture – but one in which the individual blocks, or enzymes, can only fit together in a certain way.
Then they put the enzymes they want inside E. coli bacteria. The enzymes self-assemble (by snapping together like LEGO bricks), and create the molecules needed for drug development. By piggybacking on nature, Williams and his team can quickly and inexpensively create huge numbers of different kinds of molecules that they can test, to find out which ones are the most effective against the diseases they want to treat.
Matthew Draelos and Taylor Courtney are both undergraduates doing work in the Williams lab. Draelos is a senior majoring in chemistry and biochemistry. He’s been part of the Williams lab since his freshman year.
“I came to NC State because I knew I wanted to do research and had heard it was easy to do undergraduate research here,” he says. “What captured my imagination about Williams’ research was that it’s both basic research and it’s medically relevant – we’re creating enzyme ‘mutants’ that have practical uses in creating new drugs.”
Courtney, a junior who is also majoring in chemistry and biochemistry, has only been with the lab for a few months, although she has previous research experience. “This kind of chemical biology meets a growing need in drug discovery, and I want to pursue this research in graduate school, so it’s a great opportunity for me,” she says.
Both students were encouraged to jump into the research from day one.
“You get trained to become a full partner in the lab,” Draelos says. “From the beginning I learned how to do DNA extraction, purification and analysis to make sure that we had what we wanted in its purest form. Now I’m creating my own libraries of enzyme mutants to test for usefulness in drug development. As each year passes, you are given more leeway to pursue projects independently that contribute to the lab.”
Courtney agrees. “You are definitely a full member of this lab – not just an assistant or someone who takes care of the supplies. And you’re definitely ready for graduate school or research work when you graduate.”
Hemant Desai, who earned a B.S. in chemistry and a B.A. in chemistry this year, is one of those graduates.
“I came in as a freshman, and even when my first project didn’t quite work out, it taught me a lot. My experiences in the lab prepared me really well for the topics I’m studying now in medical school.”Read More
A new species of carnivorous dinosaur – one of the three largest ever discovered in North America – lived alongside and competed with small-bodied tyrannosaurs 98 million years ago. This newly discovered species, Siats meekerorum (pronounced see-atch), was the apex predator of its time, and kept tyrannosaurs from assuming top predator roles for millions of years.
Named after a cannibalistic man-eating monster from Ute tribal legend, Siats is a species of carcharodontosaur, a group of giant meat-eaters that includes some of the largest predatory dinosaurs ever discovered. The only other carcharodontosaur known from North America is Acrocanthosaurus, which roamed eastern North America more than 10 million years earlier. Siats is only the second carcharodontosaur ever discovered in North America; Acrocanthosaurus, discovered in 1950, was the first.
“It’s been 63 years since a predator of this size has been named from North America,” says Lindsay Zanno, a North Carolina State University paleontologist with a joint appointment at the North Carolina Museum of Natural Sciences, and lead author of a Nature Communications paper describing the find. “You can’t imagine how thrilled we were to see the bones of this behemoth poking out of the hillside.”
Zanno and colleague Peter Makovicky, from Chicago’s Field Museum of Natural History, discovered the partial skeleton of the new predator in Utah’s Cedar Mountain Formation in 2008. The species name acknowledges the Meeker family for its support of early career paleontologists at the Field Museum, including Zanno.
The recovered specimen belonged to an individual that would have been more than 30 feet long and weighed at least four tons. Despite its giant size, these bones are from a juvenile. Zanno and Makovicky theorize that an adult Siats might have reached the size of Acrocanthosaurus, meaning the two species vie for the second largest predator ever discovered in North America. Tyrannosaurus rex, which holds first place, came along 30 million years later and weighed in at more than twice that amount.
Although Siats and Acrocanthosaurus are both carcharodontosaurs, they belong to different sub-groups. Siats is a member of Neovenatoridae, a more slender-bodied group of carcharodontosaurs. Neovenatorids have been found in Europe, South America, China, Japan and Australia. However, this is the first time a neovenatorid has ever been found in North America.
Siats terrorized what is now Utah during the Late Cretaceous period (100 million years ago to 66 million years ago). It was previously unknown who the top meat-eater was in North America during this period. “Carcharodontosaurs reigned for much longer in North America than we expected,” says Zanno. In fact, Siats fills a gap of more than 30 million years in the fossil record, during which time the top predator role changed hands from carcharodontosaurs in the Early Cretaceous to tyrannosaurs in the Late Cretaceous.
The lack of fossils left paleontologists unsure about when this change happened and if tyrannosaurs outcompeted carcharodontosaurs, or were simply able to assume apex predator roles following carcharodontosaur extinction. It is now clear that Siats’ large size would have prevented smaller tyrannosaurs from taking their place atop the food chain.
“The huge size difference certainly suggests that tyrannosaurs were held in check by carcharodontosaurs, and only evolved into enormous apex predators after the carcharodontosaurs disappeared,” says Makovicky. Zanno adds, “Contemporary tyrannosaurs would have been no more than a nuisance to Siats, like jackals at a lion kill. It wasn’t until carcharodontosaurs bowed out that the stage could be set for the evolution of T. rex.”
At the time Siats reigned, the landscape was lush, with abundant vegetation and water supporting a variety of plant-eating dinosaurs, turtles, crocodiles, and giant lungfish. Other predators inhabited this ecosystem, including early tyrannosaurs and several species of other feathered dinosaurs that have yet to be described by the team. “We have made more exciting discoveries including two new species of dinosaur,” Makovicky says.
“Stay tuned,” adds Zanno. “There are a lot more cool critters where Siats came from.”Read More