January 31, 2002

DAS SARMA, MORE SALT, ADDED TO UMBI'S 'EXTREME TEAM'

BALTIMORE, Md.--Salt-loving micro-organisms often "paint" the water bright red, orange and purple in parts of the Great Salt Lake, Dead Sea and other salty wet places. While tourists may snap nice travel shots, Shil DasSarma sees much more in the colorful salty Seas.

Studies by the University of Maryland Biotechnology Institute's (UMBI) newest microbial geneticist show that one-celled, "salt bugs" may hold the biological tickets to interplanetary discoveries, food crops on salty soils, better vaccines for AIDS and other diseases, new antibiotics, faster computers, clues to unsolved mysteries of biology, and a clearer understanding of evolution.

By coming to UMBI's Center of Marine Biotechnology (COMB), DasSarma (http://zdna2.umbi.umd.edu/~dassarma) has joined one of the world's leading extremophile research teams according to the National Science Foundation (NSF). Extremophiles are life forms living in conditions that humans consider inhospitable, including too salty, acidic, alkaline, high or low temperatures, high pressure, high radiation or lack of oxygen.

"We were very fortunate to hire someone who is widely considered the world's best halophile investigator," says COMB Director Yonathan Zohar. "Shil and his laboratory group put COMB more firmly at the forefront of extremophile sciences." DasSarma has spent the past 22 years in Massachusetts with MIT, the Harvard Medical School and the University of Mass. at Amherst, and has collaborated with COMB for several years.

Of the different kinds of extremophiles, salt-loving microbes or halophiles may have the most potential in industry and medicine, says DasSarma. "Halophiles are excellent for biotechnology because they are easily manipulated cell factories that need concentrated sea water and desert, two commodities in plentiful supply on our planet." Such halophile microbes use sunlight to make energy. The light sensitivity of the red byproduct may be potentially useful to increase information storage for computers.

Halophiles are also relatively easy to culture in the laboratory and harmless to humans. Thus, they are useful for teaching biological principles in colleges and grade school, he says.

Inside the single cell of a type of halophile called Halobacterium, some metabolic aspects are similar to systems in higher organisms, or eukaryotes, especially in the way genes turn on and off. Such sophisticated DNA systems had not previously been seen in a primitive organism, says DasSarma.

Last summer, DasSarma led an international consortium of scientists to complete the first genome sequence of Halobacterium NRC-l (Proceedings of the National Academy of Science, October 2001). Halobacterium is already widely used by molecular biologists as an experimental model cell. Completing its gene sequence is advancing understanding of how more complex organisms manage cell growth and division and how cells transport proteins across membranes.

Just how proteins slip across biological membranes is critical in designing effective vaccines and antibiotics, including programs at the Medical Biotechnology Center and Institute of Human Virology, two of UMBI's five biotechnology research centers across Maryland.

"No one else has centers set up like UMBI. The chance for such collaboration is here everyday," comments DasSarma. His group at COMB is working with medical researchers at UMBI and University of Mass. to determine how genes and proteins involved with controlling unusual gas bubbles in the cells of Halobacterium might be useful in delivering antigens for an orally administered AIDS vaccine. The bubbles use 13 or 14 genes to regulate cell buoyancy that help allow the microbe to survive in water over ten times saltier than seawater. Halophiles use special enzymes as catalysts to help them combat tremendous osmotic pressure of very salty habitats.

Many such enzymes of extremophiles-their sort of cellular survival kits--are highly attractive to industry for developing a wide array of products to be used in harsh conditions ranging from detergents to paper pulp processing.

Halophile enzymes are also of interest to agriculture. In California and other states, North Africa, Southeast Asia and elsewhere, repeated use of flow and sprinkler irrigation leaves the soil too salty for the best growth of rice and other crops. However, genetic engineering of certain enzymes from Halophiles may make it possible to grow better crops in salty soil.

Also, DasSarma says genome studies of Halobacterium will reveal new understanding of evolution. Many halophiles, including Halobacterium NCR-1, are members of the third branch of life, Archaea, after the Eukaryotic (true cells) and Bacterial branches. Archaea are relics of ancient forms of life. While some metabolic systems resemble Eukaryotes, a large fraction of archaeal genes seem to be unique and traceable to early Earth life.

Such genomic information might also be used to investigate whether inhospitable planets like Mars once harbored halophilic life. DasSarma says, "There are people who say that halophiles will help determine if organisms are there that are halophilic."

DasSarma adds considerable experience and credentials in diverse extremophile research to the COMB faculty, and particularly with halophiles. He has co-authored about 80 scientific publications. He was a student of Nobel Laureate H. Gobind Khorana and Uttam L. RajBhandary in the Department of Biology at Massachusetts Institute of Technology where he received his Ph.D. in biochemistry, after earning a B.S. with honors in chemistry from Indiana University. He is a member of the National Institutes of Health Study Section on Microbial Physiology and Genetics and served as Director of NSF's Metabolic Biochemistry Program.

His past and current studies include transposable elements that cause genetic variability, DNA rearrangements in chromosomes and plasmids, genome mapping and sequencing, structure, transcription and regulation of photosynthetic and buoyancy genes, gene regulation by oxygen and light, left-handed Z-DNA, DNA replication and computer applications in molecular biology.

NSF has awarded DasSarma with a $600,000 grant to sequence a second halophile, Haloarcula marismortui, in collaboration with the Institute for Systems Biology, and he brings with him to UMBI grants of nearly an additional $1 million for extremophile investigations.