麻豆影院

鈥業 managed to get pretty lucky,鈥� student says of research, Nature paper

It was not particularly surprising to learn this fall that Tom Cech and Leslie Leinwand had found a new target for anti-cancer drug development, or that the finding was published in the prestigious journal Nature.

After all, Cech, a 麻豆影院 distinguished professor of chemistry and biochemisty, is a Nobel laureate. Leinwand, a professor of molecular, cellular and developmental biology, has been a Howard Hughes Medical Institute investigator and an elected fellow of the American Association for the Advancement of Science.

Given these researchers鈥� stature鈥攁nd the fact that they lead CU鈥檚 cutting-edge BioFrontiers Institute鈥攊t might come as a revelation that one of the co-authors on the Nature paper was, at the time of her participation in the project, an undergraduate student.

She is Caitlin F. Bell, now a medical student at Vanderbilt University. Recently, she talked about what it was like to work with scientists whose names are usually uttered in reverential tones.

Bell started doing 鈥済runt work鈥� in Cech鈥檚 lab during her freshman year. 鈥淚 like to think that I just didn鈥檛 break too much stuff in the process of doing that.鈥�

The summer after her first year, she began working with a post-doctoral researcher, Jayakrishnan Nandakumar, who was working on the project at the time and was first author on the Nature paper. She stayed on.

Nandakumar, who is a Howard Hughes Medical Institute research fellow, was an inspiration and wonderful to work with, Bell said. Nandakumar and Cech conceived of the project.

鈥淚 managed to get pretty lucky,鈥� Bell said. She worked on the research project through the remainder of her undergraduate career at CU-麻豆影院. In May, she graduated with distinction with a degree in MCDB.

Her graduation roughly coincided with the time the paper was submitted to Nature, which is among the top four scientific journals (as rated by the frequency their articles are cited in subsequent research).

In the Nature paper, the scientists detailed a new target for anti-cancer drug development that sits at the ends of our DNA.

Researchers in the two laboratories collaborated to find a patch of amino acids that, if blocked by a drug docked onto the chromosome end at this location, may prevent cancerous cells from reproducing. The amino acids at this site are called the 鈥淭EL patch鈥� and once modified, the end of the chromosome is unable to recruit the telomerase enzyme, which is necessary for growth of many cancerous cells.

鈥淭his is an exciting scientific discovery that gives us a new way of looking at the problem of cancer,鈥� Cech said. 鈥淲hat is amazing is that changing a single amino acid in the TEL patch stops the growth of telomeres. We are a long way from a drug solution for cancer, but this discovery gives us a different, and hopefully more effective, target.鈥�

Cech is the director of the BioFrontiers Institute, a Howard Hughes Medical Investigator and winner of the 1989 Nobel Prize in chemistry. Leinwand is chief scientific officer of the BioFrontiers Institute and holds a joint appointment at the CU-Denver School of Medicine; she is also the winner of the National Heart, Lung and Blood Institute MERIT Award.

Other co-authors on the study include postdoctoral fellow Ina Weidenfeld and Howard Hughes Medical Institute Senior Scientist Arthur Zaug.

Telomeres have been studied since the 1970s for their role in cancer. They are constructed of repetitive nucleotide sequences that sit at the ends of our chromosomes like the ribbon tails on a bow.

This extra material protects the ends of the chromosomes from deteriorating, or fusing with neighboring chromosome ends. Telomeres are consumed during cell division and, over time, will become shorter and provide less cover for the chromosomes they are protecting. An enzyme called telomerase replenishes telomeres throughout their lifecycles.

Telomerase is the enzyme that keeps cells young. From stem cells to germ cells, telomerase helps cells continue to live and multiply. Too little telomerase produces diseases of bone marrow, lungs and skin. Too much telomerase results in cells that over proliferate and may become 鈥渋mmortal.鈥� As these immortal cells continue to divide and replenish, they build cancerous tumors. Scientists estimate that telomerase activation is a contributor in up to 90 percent of human cancers.

To date, development of cancer therapies has focused on limiting the enzymatic action of telomerase to slow the growth of cancerous cells. With their latest discovery, Cech and Leinwand envision a cancer drug that would lock into the TEL patch at chromosome ends to keep telomerase from binding there.

This approach of inhibiting the docking of telomerase may be the elegant solution to the complex problem of cancerous cells. Cech, a biochemist, and Leinwand, a biologist, joined forces to work on their latest solution.

Most of Bell鈥檚 research involved the relationship between the TEL patch and telomerase in bacteria.

鈥淚 did a lot of cloning and genetic manipulation. I was lucky enough to be trained by them to do a variety of different tests using the protein that I made.鈥�

There were strong indications that the patch existed. 鈥淭he results ended up looking a lot prettier than we expected,鈥� Bell said.

鈥淚t was almost too pretty to be true.鈥�

As a medical student, Bell is weighing her career options. 鈥淚 really enjoyed the research that I did, and I miss it,鈥� she said. 鈥淚鈥檇 like to find a way to combine research and clinical work.鈥�

Cech has offered good career advice, she noted.

鈥淗e鈥檚 fantastic,鈥� she said. 鈥淓ven if I had dumb questions for him, it was always possible to get an appointment and go talk with him. He鈥檚 a very good teacher, and his love of teaching you can also see in the lab.鈥�

Cech returned the compliment:

鈥淐aitlin is smart, poised and very tenacious.听She is talented at time-management: one moment she鈥檚 doing an experiment in the lab, the next she鈥檚 organizing a clinic in Ecuador to provide medical care in an impoverished area, all in her 鈥榮pare time鈥� between classes.鈥�

Cech also said involving undergraduate students in such research projects allows students to explore the unknown, asking real-world questions using state-of-the-art instrumentation.

He added: 鈥淭his is the most engaging, most transformative, and most career-oriented education that we give our undergraduates!鈥澨齀t does carry a cost, given that neither the university nor the state has much support for this sort of education, Cech said. 鈥淪o the individual lab heads have to write grants to get funds from national sources to pay summer student stipends and consumable supplies.鈥�

Though she鈥檚 already been published in Nature, Bell said her fellow first-year medical students don鈥檛 comment much about it.

鈥淚 haven鈥檛 told many people.鈥�

Emilia Costales at the听BioFrontiers Institute听contributed to this report.