Two of the most prestigious prizes in biology were recently awarded to Hopkins scientists. Andrew Fire shared the Nobel Prize in Physiology or Medicine for his discovery of RNA interference. Carol Greider shared the Albert Lasker Award for Basic Biomedical Research, often described as the "American Nobel," for her work on the enzyme telomerase.
Fire is a professor at Stanford University and an adjunct professor in the Biology Department on Homewood campus, a post he has held since becoming an investigator at the Carnegie Institution in 1989. He shares the Nobel prize with Craig Mello of the University of Massachusetts.
Greider is the director of molecular biology and genetics at the Johns Hopkins Institute of Basic Biomedical Sciences on the medical campus. She shares the Lasker Award with her doctoral mentor, Elizabeth Blackwell of the University of California, San Francisco, as well as Jack Szostak of Harvard Medical School.
RNA interference (RNAi) and telomerase are natural regulatory mechanisms found in many cell types across all kingdoms of life. Both mechanisms have been discovered and explained relatively recently, and both have opened tremendous opportunities in basic and clinical biology.
RNAi involves the machinery cells use to translate genes into proteins. When a cell wants to produce a certain protein, it transcribes the corresponding DNA sequence into a shorter molecule called messenger RNA (mRNA). This mRNA then serves as a template for translation.
In RNAi, which was discovered by Fire and Mello in 1998 when both were working at the Carnegie Institution on Homewood campus, a cell takes advantage of the structure of mRNA to prevent certain genes from being expressed. Every mRNA molecule has a complementary strand, a particular sequence of nucleotides that can precisely pair up with it and therefore block its activity. The coding mRNA and interfering RNA molecules pair up into an inactive double-stranded molecule.
Several types of plant and animal cells routinely use native RNAi to silence genes in real time. This process helps the cells regulate which proteins are produced at any given moment, and can further alter the quantity and rate of protein production.
RNAi is also recognized as a powerful experimental tool. If researchers can design an RNA molecule complementary to an mRNA of interest, they can introduce it into the cell and therefore block the expression of that protein. This allows scientists to determine the biological functions of each protein without altering the DNA of the cell.
Several groups are now working on clinical applications of RNAi. Many illnesses, such as the genetic brain disorder Huntington's disease, are associated with the overproduction of specific proteins, which could be blocked by RNAi. Additionally, RNAi is being researched as a means to hinder the expression of viral proteins necessary for many infectious diseases.
Telomerase is an enzyme associated with the regulation of chromosomal DNA across many generations. Chromosomes in eukaryotes, which includes all plants and animals, are capped by a long repeating string of DNA, called a telomere. This sequence is shortened each time the chromosome duplicates and the whole cell divides.
The shortening of chromosomal ends is a natural by-product of the DNA replication process. However, if the telomeric sequence shortens too much over several cell cycles, the chromosome itself would be at risk of degradation. Many cells ultimately die if too much telomeric sequence is lost.
Telomerase works to counter the shortening of telomeres by adding extra nucleotides to the telomere each time the chromosome replicates. It was discovered in 1984 by Greider, then a graduate student with Blackburn at UC Berkeley, and the first paper on it was published in December 1985.
Although telomerase was initially described by Greider in the single-celled organism Tetrahymena, subsequent studies soon discovered it in virtually all species, including mammals. Telomerase helps preserve the integrity of chromosomes across several generations of cells.
Telomerase is now known to be involved in several pathways associated with cancer, aging, and stem cells. For instance, defective telomerase can allow cancer cell lines to divide repeatedly, effectively causing them to become "immortal." Cancer treatments that target telomerase are currently being investigated.
Since aging is often associated with the accumulation of random mutations and structural damage in DNA, it might be expected that the capping of chromosomes with telomeres might help slow the aging process. In fact, a smaller-scale process of aging called "cellular senescence" is known to be dependent on telomeres and telomerase.
Stem cells, which must divide many times in order to differentiate into other cell types, require telomerase to prevent chromosomal degradation. Greider and colleagues have recently discovered that mutations in telomerase are the cause of a rare disease called dyskeratosis congenita, in which stem cells in bone marrow are unable to survive and differentiate.
The Nobel Prize is awarded each year in honor of Alfred Nobel, a Swedish inventor who died in 1896 and left his estate to establish a series of awards given to those who "have conferred the greatest benefit on mankind." The awards in chemistry, physics, medicine or physiology, literature, peace, and (since 1969) economics are generally considered the greatest honors in each field.
Alfred Lasker, an American businessman, and his wife, Mary Woodard Lasker, established the prestigious Lasker Awards in 1946 to honor scientists in biomedicine. The four categories of the award are basic medical research, clinical medical research, public service and special achievement. These honors are often considered "American Nobels," as they are awarded after rigorous review by a select panel of eminent scientists. Over 70 of the award's recipients have subsequently won Nobel Prizes.
Blake Hill, an associate professor in the biology department, praised his colleague. "It's wonderful to see the people you admire and respect the most do well, and that is exactly what has happened with the awarding of the Nobel Prize in Medicine to Andy Fire.
"Many folks speculated that it was just a matter of time before Andy was awarded the Nobel Prize. The reason for this speculation was clear: Andy's research fundamentally changed the way we think about gene regulation. He is exactly the type of person you want to see win the Nobel Prize: a nice guy who is thoughtful, considerate, and insightful."
Greider initially thought it was a joke when she was called with the news of her award. "My first reaction was one of surprise. They are supposed to call you when you win, but since it was late in a day I received an email instead. It was not until later that I received the call."
She added that basic research has great possibilities. "This is really an example of, you never know where basic research will go. We had to trust that understanding those pathways will help understand disease as well."