|Bacterial Molecular Genetics and Biotechnology
Dr. Benedik is not currently accepting new students.
My laboratory studies basic biological problems using molecular genetic methods with simple microbial systems. Additionally we are developing novel microbial approaches for biotechnological applications.
Biotechnology/Bioremediation - Cyanide
The aim of this project is better enzymes for degrading cyanide in waste streams and contaminated sites. The industrial uses of cyanide have resulted in contamination at many sites, especially the water and soil of metal plating plants and as the result of ore extraction in mining operations. Especially in light of recent highly-publicized incidents of cyanide contamination (e.g., in Houston-area plating facilities as well as the recent cyanide release in Eastern Europe) there is a need to develop lower-cost, efficient methods to detoxify these sites. Cyanide is a common constituent of biological systems and is actually produced by a variety of organisms, especially plants. Due to the toxicity of cyanide, nature has evolved numerous biochemical pathways for its conversion to innocuous byproducts. There is previous work on biodegradation of cyanide, either by enzymes or metabolically-active whole cells, using a variety of different pathways. The most interesting for our project are those cyanide-degrading enzymes which can function without the need for active cellular metabolism, and can be used under conditions which would kill microorganisms.
We hope to apply modern molecular biology to improve the cost, stability, and metal-tolerance of cyanidases, enzymes which convert cyanide directly to formate and ammonia. These end products are vastly less toxic than cyanide, and they can also be directly metabolized by indigenous microorganisms to cell mass, CO2, and water. Like other enzymes, cyanidases are capable of scavenging and destroying their substrate (i.e., cyanide) down to extremely low levels (< 0.01 ppm). Cyanidases have already been applied to cyanide removal, but the commercial technology is relatively old, and has not taken advantage of: (1) the ability to overexpress enzyme activities in alternative hosts, (2) opportunities for functional improvement by protein engineering, and (3) the discovery and cloning (by others in the literature) of new forms of this enzyme with potentially superior properties.
Our work is leading to further insights on the structural biology of this important branch of nitrilase enzymes as well as in the development of novel enzymes for industrial applications in bioremedation.
Bacterial Persistence and Antibiotic Tolerance
Antibiotics are effective at killing most bacteria, however for any large population there are always a small number of survivors no matter how long the treatment is administered. These bacterial cells that survive antibiotic treatment are called persisters and the phenomenon of bacterial persistence is long-standing. The project aims to elucidate the molecular mechanisms of dormancy in bacteria where bacteria are not killed by antibiotics but rather persist throughout treatment and awaken after the antibiotic therapy ceases. This leads to disease recurrence as well as increased antimicrobial resistance. The project aims to understand the signals that lead to the dormant state and eventually to develop therapeutic interventions that can “wake” these bacteria before antibiotic therapy ceases.