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DESCRIPTION OF INTERESTS
Our laboratory uses molecular biological and biochemical approaches to study two projects focusing on the parasitic protozoan, Trypanosoma brucei. The first project centers on the mitochondrial ATP synthase of T. brucei. This protein complex couples the energy generated by the electron transport chain to the synthesis of ATP. In T. brucei we have shown that the ATP synthase is regulated through the life cycle of the organism by several unique mechanisms which appear to be different from the regulatory mechanisms for other mitochondrial proteins such as those in the electron transport chain. This regulation may be critical to understanding how this parasite responds to change in the environment due to the two host organisms (in this case, the tsetse fly and the cow). We have isolated the ATP synthase and have cloned several genes for component subunits of the complex. We have shown a differential regulation of these subunits at the level of mRNA stability and are now examining the specific sequences and
nucleic acid binding proteins involved in this regulation. We are using RNA interference to create genetic knock downs as a tool to understanding the role of the ATP synthase in the parasites survival in its hosts.
The second project, in collaboration with Dr. William Ruyechan, examines a pair of unique RNA binding proteins, p34 and p37, which are highly homologous to one another. We have shown that these proteins interact with 5 S rRNA and hypothesize that they act to chaperone the 5 S rRNA from the nucleus where it is synthesized by RNA polymerase III, to the nucleolus for assembly with other ribosomal components. We have also identified a family of nucleolar phosphoproteins, the NOPP44/46 proteins, that interact with the p34 and p37 proteins, and may assist in this process of 5S rRNA migration. The p34 and p37 proteins show developmentally regulated expression through the life cycle of T. brucei. Most interestingly, the regulation of the two proteins are exactly opposite one another making them an excellent target to examine developmentally regulated genes. Expression of the smaller of the two proteins, p34, is regulated by differential mRNA stability and we have found two AU rich sequence elements present in the 3‘
untranslated region of this transcript that may be responsible. These AU rich elements have been shown in higher eukaryotes to be involved in both transcript stability and translational regulation. In constrast, expression of the larger protein, p37, is regulated translationally, possibly by sequences in the 3‘ untranslated region as well. In addition, we have found that the p37 protein is specifically degraded in the procyclic stage of the parasite and are currently characterizing the protease responsible for this process.
In collaboration with Dr. Beatriz Garat, Universidad de la Républica, Dept. of Biochemistry, Montevideo, Uruguay, we are examining proteins which bind to dinucleotide repeats occurring in the intergenic regions of the genome of Trypanosoma cruzi. This project, which is funded by the Fogarty Foundation, examines whether these repeats together with their cognate binding proteins may be involved in gene regulation in T. cruzi.
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SPECIALTIES
Infectious Disease
Microbiology
Microbial Pathogenesis
Molecular basis of disease and Parasitology
Regulation of gene expression
Regulation of metabolism
Regulation of transcription and translation
Microbial Pathogenesis
Molecular basis of disease and Parasitology
Regulation of gene expression
Regulation of metabolism
Regulation of transcription and translation |
EDUCATION
| 1981 |
Doctor of Philosophy, Biochem/Mol. Biol.
New York University
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| 1977 |
Bachelor of Science, University of Maine
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PUBLICATIONS
| Duhagon, M.A., Dallagiovanna, B., Ciganda, M., Ruyechan, W., Williams, N., and Garat, B; A novel type of single-stranded nucleic acid binding protein recognizing a highly frequent motif in the intergenic regions of Trypanosoma cruzi; Biochem. Biophys. Res. Commun; 2003 Jan; 309; 183-188 |
| Li, J., Ruyechan, W.T., and Williams, N.; Stage specific translational efficiency and protein stability regulate the developmental expression of p37, an RNA binding protein from Trypanosoma brucei.; Biochem. Biophys. Res. Commun; 2003 Jan; 306; 918-923 |
| Pitula, J., Park, J., Parsons, M., Ruyechan W, Williams N; Two families of RNA binding proteins from Trypanosoma brucei associate in a direct protein-protein interaction; Mol. Biochem. Parasit.; 2002 Jan; 122; 81-89 |
| Pitula J, Ruyechan WT, Williams N; Two Novel RNA Binding Proteins from Trypanosoma brucei Are Associated with 5S rRNA.; Biochem Biophys Res Commun; 2002 Jan; 290(1); 569-576 |
| Brown B SV, Chi TB, Noreen Williams; The Trypanosoma brucei mitochondrial ATP synthase is developmentally regulated at the level of transcript stability.; Mol Biochem Parasitol; 2001 Jul; 115(2); 177-187 |
| Brown B SV, Stanislawski A, Perry QL, Noreen Williams; Cloning and characterization of the subunits comprising the catalytic core of the Trypanosoma brucei mitochondrial ATP synthase.; Mol Biochem Parasitol; 2001 Apr; 113(2); 289-301 |
| Hellman, K., William Ruyechan, Noreen Williams; Characterization of the RNA binding properties and protein-protein interactions of p34 and p37 from Trypanosoma brucei; RNA Society Meeting, Banff, Alberta; 2001 Jan; |
| Li, J., William Ruyechan, Noreen Williams; Differential regulation of two homologous nucleic acid binding proteins in T. brucei, p34 and p37; 2nd Internatioinal Conference on proteins that Bind RNA, Austin/Lake Travis, Texas; 2001 Jan; |
| Li, J., William Ruyechan, Noreen Williams; Differential regulation of two homologous RNA binding proteins in T. brucei, p34 and p37; RNA Society Meeting, Banff, Alberta; 2001 Jan; |
| Li, J., William Ruyechan, Noreen Williams; Differential regulation of two homologous RNA binding proteins in Trypanosoma brucei, p34 and p37; RNA Society Meeting, Madison, Wisconsin; 2000 Jan; |
| Pitula, J., William Ruyechan, Noreen Williams; Two families of RNA binding proteins from Trypanosoma brucei associate in a complex which contains 5S rRNA; RNA Society Meeting, Madison Wisconsin; 2000 Jan; |
| Brown SV, Noreen Williams; Analysis of the 60 S ribosomal protein L27a (L29) gene of Trypanosoma brucei.; Int J Parasitol; 1999 May; 29(5); 731-736 |
| Pitula, J., William Ruyechan, Noreen Williams; Two novel RNA binding proteins from Trypanosoma brucei; RNA Society Meeting, Edinburgh, Scotland; 1999 Jan; |
| Zhang, J., William Ruyechan, Noreen Williams; Developmental regulation of two nuclear RNA binding proteins, p34 and p37, from Trypanosoma brucei; Mol. Biochem. Parasitol.; 1998 Jan; 92; 29-38 |
| Fuenmayor, J., Zhang, J., William Ruyechan, Noreen Williams; Identification and characterization of two DNA polymerase activities present in Trypanosoma brucei mitochondria; J. Euk. Microbiol.; 1998 Jan; 45; 404-410 |
| Chi, T.B., Brown, S.V., Noreen Williams; Subunit 9 of the Mitochondrial ATP synthase of Trypanosoma brucei is nuclearly encoded and developmentally regulated; Mol. Biochem. Parasitol.; 1998 Jan; 92; 29-38 |
| Pitula, J., William Ruyechan, Noreen Williams; T. brucei: identification and purification of a poly A binding protein; Exp. Parasitol.; 1998 Jan; 88; 157-160 |
| Zhang J, Williams N; Purification, cloning, and expression of two closely related Trypanosoma brucei nucleic acid binding proteins.; Mol Biochem Parasitol; 1997 Aug; 87(2); 145-158 |
| Brown, S.V., Noreen Williams; Regulation of the Trypanosoma brucei ATP synthase beta subunit; FASEB J.; 1997 Jan; 11; A1084 |
| Chi TB, Choi SY, Williams N; The ATP synthase of Trypanosoma brucei is developmentally regulated by an inhibitor peptide.; Arch Biochem Biophys; 1996 Sep; 333(1); 291-297 |
| Zhang, J., William Ruyechan, Noreen Williams; Characterization of Trypanosoma brucei Single-Strand Nucleic Acid Binding Proteins p34 and p37; Global Meeting on Parasitic Disease, New Delhi, India; 1996 Jan; |
| Sondej, M., Noreen Williams; Regulation of the Mannose Phosphotransferase System in Escherichia coli; 95th ASM General Meeting; 1995 Jan; |
| Brown, S.V., Chi, T.B., Tanaka, M., Noreen Williams; The Mitochondrial ATP Synthase of Trypanosoma brucei: Regulation and Genetic Mapping; Biophys. J.; 1995 Jan; 68; A257 |
| Williams N; The mitochondrial ATP synthase of Trypanosoma brucei: structure and regulation.; J Bioenerg Biomembr; 1994 Apr; 26(2); 173-178 |
| Noreen Williams; The mitochondrial ATP synthase of Trypanosoma brucei: Structure and regulation; J. Bioenerg. Biomemb.; 1994 Jan; 26; 173-178 |
| William Ruyechan, Noreen Williams; DNA binding Proteins of Trypanosoma brucei; International Congress of Protozoology, Berlin, Ge rmany; 1993 Jan; |
| Noreen Williams; Regulation and Characterization of the Trypanosoma brucei ATP Synthase; International Congress of Protozoology Reports, Berlin, Germany; 1993 Jan; |
| Sondej, M., Noreen Williams; The Escherichia coli Pel Protein: Its Role in lambda Phage Penetration and Mannose Transport; 93rd ASM General Meeting; 1993 Jan; |
| Noreen Williams, Frank, P.H.; Developmental Regulation and Characterization of the Trypanosoma brucei ATP Synthase; Biophys. J.; 1992 Jan; 61; A118 |
| Noreen Williams, Frank, P.H.; The mitochondrial ATP synthase from Trypanosoma brucei; 6th EBEC Meetings Short Reports, Noordwijkerhout, The Netherlands; 1990 Jan; |
| Noreen Williams, Frank, P.; The mitochondrial ATP synthase of T. brucei: Isolation and characterization of an intact F1 Moiety; Molec. Biochem. Parasitol.; 1990 Jan; 43; 125-132 |
| Noreen Williams, Frank, P.H.; The mitochondrial ATP synthase of Trypanosoma brucei; Biophys. J.; 1990 Jan; 57; 202a |
| Noreen Williams, Hullihen, J., Pedersen, P.L.; Mitochondrial ATP synthase: Role of metal binding in structure and function; Ion Pumps: Structure, Function and Regulation; 1988 Jan; |
| Noreen Williams, Hullihen, J., Pedersen, P.L.; Ligand binding studies of the F1 moiety of rat liver ATP synthase - implications about its structure, active sites and mechanism of action; Biochem.; 1987 Jan; 26; 162-169 |
| Pedersen, P.L., Noreen Williams, Hullihen, J.; Mitochondrial ATP synthase: Dramatic magnesium induced alterations in the structure and function of the F1-ATPase moiety; Biochem.; 1987 Jan; 26; 8631-8637 |
| Noreen Williams, Fox, D.K., Shea, C., Roseman, S.; Pel, the protein that permits lambda DNA penetration of Escherichia coli, is encoded by a gene in ptsM and is required for mannose utilization by the phosphotransferase system; Proc. Nat. Acad. Sci.; 1986 Jan; 83; 8934-8938 |
| Pedersen, P.L., Noreen Williams, Hullihen, J.; Relationship of ligand binding properties of ATP synthase (F1) of rat liver to the enzyme structure and mechanism; 4th EBEC Meeting Short Reports, Prague, Czechoslovakia; 1986 Jan; |
| Noreen Williams, Fox, D.K., Roseman, S.; The E. coli mannose phosphotransferase system (PTS): Molecular cloning and identification pf products of the ptsM locus; Fed. Proc.; 1986 Jan; 45; 1760 |
| Noreen Williams, Pedersen, P.L.; Magnesium binding to the purified F1-ATPase of rat liver mitochondria -Implications for function; Biophysical J.; 1985 Jan; 47; 487a |
| Kaplan, R.S., Noreen Williams, Hullihen, J., McEnery, M., Nakashima, R.A., Paggi, M., Pedersen, P.L.; Anion transport, ATP synthesis, and ATP export in liver mitochondria-Recent progress on molecular components catalyzing these processes; Short Reports of the Third EBEC Meeting, Hanover, Germany; 1984 Jan; A; 345-349 |
| Noreen Williams, Amzel, L. M., Pedersen, P.L.; Proton ATPase of rat liver mitochondria: A rapid procedure for purification of a stable, reconstitutively active F1 preparation using a modified chloroform method; Anal. Biochem.; 1984 Jan; 140; 581-588 |
| Noreen Williams, Hullihen, J., Pedersen, P.L.; The proton adenosine triphosphatase complex of liver mitochondria. Temperature dependent dissociation-reassociation of the F1-ATPase subunits; Biochem.; 1984 Jan; 223; 780-785 |
| Noreen Williams, Pedersen, P.L.; Structure of the H+-ATPase of liver mitochondria: Interaction of the gamma subunit with both the alpha and beta subunits; Biophysical J.; 1983 Jan; 41; 323a |
| Noreen Williams, Coleman, P.S.; Exploring the adenine nucleotide binding sites on mitochondrial F1-ATPase with a new photoaffinity probe 3'-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate; J. Biol. Chem.; 1982 Jan; 257; 2834-2841 |
| Coleman, P.S., Noreen Williams; Probing the mechanism of the rat liver F1-ATPase by benzoyl ATP; Biophysical J.; 1982 Jan; 37; 404a |
| Noreen Williams, Coleman, P.S.; Photoaffinity labelling of specific subunits of mitochondrial F1-ATPase by benzoylbenzoic ATP; Fed. Proc.; 1981 Jan; 40; 65 |
| Noreen Williams, Coleman, P.S.; Benzophenone derivatives of adenine nucleotides as new photoaffinity probes for the F1-ATPase binding site studies; Fed. Proc.; 1980 Jan; 39; 1844 |
GRANTS
March 2002 to February 2007
Biogenesis of the T. brucei Mitochondrial ATP Synthase
NIH
Noreen Williams
$1,537,920
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September 2001 to August 2006
Training-Infectious Disease, Microbiology, and Immunology for Medical Students
State University of New York at Buffalo
T. Murphy
$213,900
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July 2001 to June 2004
Single-stranded Binding Proteins in Trypanosoma cruzi
NIH/Fogarty FIRCA
Noreen Williams
$118,108
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July 2001 to June 2002
UB Graduate Group Award
Buffalo DNA Replication Graduate Group
Thomas Melendy, William Ruyechan, Noreen Williams
$3,000
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July 1999 to June 2004
Training in Microbial Pathogenesis
National Institute of Allergy and Infectious Diseases
John Hay, Noreen Williams
$856,496
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April 1999 to March 2004
Developmental Regulation of DNA/RNA Binding Proteins
NIH
Noreen Williams
$885,006
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October 1998 to September 2001
RNA binding proteins in Plasmodium falciparum
NIH
Noreen Williams, Laurie Read
$230,499
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June 1997 to December 1998
RNA Binding Proteins in Plasmodium falciparum
UB Multidisciplinary Pilot Project Program
Laurie Read, Margaret Hollingsworth, Noreen Williams
$20,000
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June 1996 to May 2002
Training Program in Peridontal Disease
National Institute for Dental & Craniofacial Research
R. Genco
$1,165,033
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May 1995 to April 1996
Characterization of a Novel DNA Polymerase from Trypanosoma brucei
UB Multidisciplinary Pilot Project Program
Noreen Williams, William Ruyechan
$20,000
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January 1994 to January 1999
Markey Foundation Award
Markey Foundation Award
B. Holm and P.T. LoVerde
$1,000,000
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December 1992 to November 1999
Control and Development of Parasite Energy Metabolism
NIH
Noreen Williams
$740,665
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August 1992 to August 1995
Energy Matabolism of Trypanosoma brucei
Research Competition Award, UB Intramural
Noreen Williams
$50,000
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September 1989 to January 1993
Structure, Function, and Developmental Regulation of T. brucei
National Science Foundation
Noreen Williams
$215,000
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April 1988 to September 1991
H+-ATPase from T. brucei: Isolation and Characterization
USUHS
Noreen Williams
$103,750
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October 1987 to March 1988
H+-ATPase: Structure and Function of the Active Site
USUHS
Noreen Williams
$13,500
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