toms@ncifcrf.gov (Tom Schneider) (03/16/89)
I am looking for a hard-working postdoc with a degree in molecular biology to do bench work on an exciting project in my lab. PROJECT DESCRIPTION: Binding sites, such as the lac operator on DNA or ribosome binding sites on RNA, consist of a pattern to which a specific macromolecule---a ``recognizer''---binds. These patterns are often described by using a consensus sequence. Another way to characterize them is to determine how much information is needed to specify the pattern. For example, ribosome binding sites in E. coli can be described using 11.0 bits of information. (A bit of information is the information you would need to distinguish between two equally likely events, such as a coin flip.) The number 11 is not meaningful by itself; we need something to compare it to. Given the size of the genome and the number of binding sites, we can calculate how much information the recognizer needs to find the sites. For ribosomes in E. coli this is 10.6 bits. This means that the amount of information stored in the patterns at binding sites (11.0 bits) is just enough for the sites to be found in the genome (10.6 bits). The patterns at bacteriophage T7 promoters are a big exception. They contain about 35 bits, although only 17 bits should be needed by the RNA polymerase. If the polymerase really only uses half of the pattern information, then we should be able to destroy the other half and still have strong promoters. I synthesized, cloned and sequenced many strong T7 promoters with several basepair changes each, and showed that the polymerase uses only 18+/-2 bits. This confirms the hypothesis that the information in the pattern used by a recognizer can be predicted from the selection job that has to be done to locate the sites in the genome. The ``extra'' information in the phage genome is probably the binding site of another protein. The postdoc will continue bench work on this project. He or she must have experience in molecular biology, including cloning, sequencing and bacterial genetics. A knowledge of computers and information theory is not required. The molecular biology and computer facilities here are excellent. Two papers that describe the project are: T. D. Schneider, G. D. Stormo, L. Gold, and A. Ehrenfeucht. Information content of binding sites on nucleotide sequences. J. Mol. Biol., 188:415--431, 1986. T. D. Schneider and G. D. Stormo. Excess information at bacteriophage T7 genomic promoters detected by a random cloning technique. Nucleic Acids Research, 17:659-674 1989 STARTING DATE: immediate LOCATION: National Cancer Institute National Institutes of Health Frederick, MD KIND OF POSITION: IRTA fellowship NIH Intramural Research Training Award 1 year initial appointment, renewable for 3 years. SALARY: Years of Postdoctoral Experience upon entrance to duty determines the initial Stipend: initial 2nd year 3rd year 0 - 1 $20,000 21,500 23,000 1 - 2 $21,500 23,000 24,500 2 - 3 $23,000 24,500 26,000 The following application documents are required: a. Curriculum Vitae b. Bibliography c. 3 letters of reference emphasizing research potential d. Applicant's statement of research goals (approximately 1 page in length), and type and purpose of training desired e. Official copy of doctoral degree f. Official copy of undergraduate and graduate or medical school transcripts g. Brief summary of doctoral dissertation h. SF-171 Application Thomas Schneider National Cancer Institute Frederick Cancer Research Facility Building 469, Room 144 P. O. Box B Frederick, MD 21701 (301) 698-5581 (-5532 for messages) computer network address: toms@ncifcrf.gov