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Faculty Detail    
Name N PATRICK HIGGINS
  
Campus Address KAUL 524 Zip 0024
Phone  (205) 934-3299
E-mail  nphiggins@bmg125.cmc.uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Biochemistry & Molecular Genetics  Biochemistry & Molecular Genetics Professor Emeritus

Graduate Biomedical Sciences Affiliations
Biochemistry and Molecular Genetics Program 
Biochemistry and Structural Biology 
Cellular and Molecular Biology Program 
Integrative Genetics Graduate Program 
Waiting to be Seated 

Biographical Sketch 
Patrick Higgins completed undergraduate studies at Wichita State University. He obtained a Ph.D. degree in the Department of Microbiology from the University of Chicago (1976). He was appointed to the faculty of the University of Wyoming in 1979 and moved to Birmingham in 1984, where he is a full Professor of Biochemistry and Molecular Genetics and Co-Director of the Howell Heflin Center for Human Genetics . His research is supported through grants from the NIH, NSF, American Cancer Society, and the Parke Davis Corporation

Society Memberships
Organization Name Position Held Org Link
American Society for Biochemistry and Molecular Biology  Member  htpp://www.asmbm.org/ 
American Society for Microbiology  Member, Symposium Committee  http://asm.org/ 
American Society for the Advancement of Science  Member  http://www.aaas.org/ 
Editorial Board Journal of Biological Chemistry  Member  http://www.jbc.org/ 
Genetics Society of America  Member  http://www.genetics-gsa.org/ 
 



Research/Clinical Interest
Title
Genetic and Biochemical Studies of Chromosome Dynamics
Description
Chromosomes are organelles that maintain genetic order inside living cells. Problems in chromosome structure and function are detected as a normal process of aging and chromosome problems are a signature of numerous disease states including cancer and genetic syndromes like Downs. A chromosome is not just DNA, but a structure organized by a complex mixture of structural proteins, sequence-specific proteins, enzymes, and small RNA's. These components must work together to facilitate reactions like transcription of ribosomal RNA and mRNA, DNA replication, and homologous recombination. In addition to encoding signals for transcription and replication, chromosomes also move to specific cellular locations. Our lab studies the cellular mechanisms that govern chromosome movement using biochemical and genetic methods. One way to study DNA movement in E. coli and Salmonella typhimurium is to use site specific recombination. This method combines specially marked chromosomes with controlled expression of site specific recombinases from yeast (Flp) and the transposon (Tn3 resolvase) to measure how frequently two segments of DNA touch (Higgins et al. 1996). Experiments show that log phase bacteria have about 150 (30 kb) domains with boundaries that occur at random with respect to DNA sequence. Two enzymes that influence domain structure are DNA gyrase and Topoisomerase IV (Staczek and Higgins, 1998). Viruses that grow in bacteria are sensitive to this structure, and when bacteriophage Mu replicates it transposes from one domain to another (Mana and Higgins, 1999). Understanding the folding and movement of DNA molecules in vivo is critical for progress in understanding a wide range of topics in molecular genetics, including mechanics of recombination, replication, transcription and chromosome segregation. Current projects in the lab involve microarrays and strategies to identify special sequences that restrict chromosome movement at the origin and near the terminus of DNA replication.

Selected Publications 
Publication PUBMEDID
Staczek, P., and Higgins, N.P. (1998) DNA gyrase and Topoisomerase IV modulate chromosome domain size in vivo. Mol. Micro. 29: 1435-1448.   9781880 
Scheirer, K.E., and Higgins, N.P. (1997) The DNA cleavage reaction of DNA gyrase. Comparison of stable ternary complexes formed with enoxacin and CcdB protein. J. Biol. Chem. 272: 27202-27209.   9341164 
Higgins, N.P., Yang, X., Fu, Q., and Roth, J.R. (1996) Surveying a supercoil domain by using the ? resolution system in Salmonella typhimurium. J. Bacteriol. 178: 2825-2835.  8631670 
Manna, D., Porwollik, S., McClelland, M., Tan, R., and Higgins, N. P. (2007). Microarray analysis of Mu transposition in Salmonella enterica, serovar Typhimurium: transposon exclusion by high-density DNA binding proteins. Mol Microbiol 66, 315-328.


 		 17850262 
Higgins, N.P. (2007) Under DNA stress, gyrase makes the sign of the cross. Nat Struct Mol Biol 14: 256-258.
 		 17410088  
Champion, K., and Higgins, N.P. (2007) Growth-Rate Toxicity Phenotypes and Homeostatic Supercoil Control Differentiate E. coli from Salmonella Typhimurium. J Bacteriol 189: 5839-5849.
 		 17400739 
Higgins, N.P. (2007) Mutational bias suggests that replication termination occurs near the dif site, not at Ter sites: what's the dif? Mol Microbiol 64: 1-4.
 		 17376066  
Pang, Z., Chen, R., and Higgins, N.P. (2005) A gyyase mutant with low activity disrupts supercoiling at the replication terminus. J. Bacteriol. 187: 7773-7783.  16267301 
Deng S, Stein RA, Higgins NP. Organization of supercoil domains and their reorganization by transcription. Mol Microbiol. 2005 Sep;57(6):1511-21.   16135220 
Manna D, Deng S, Breier AM, Higgins NP. Bacteriophage Mu targets the trinucleotide sequence CGG. J Bacteriol. 2005 May;187(10):3586-8.  15866949 
Stein, R., S. Deng, and N. P. Higgins. 2005. Measuring chromosome dynamics on different timescales using resolvases with varying half-lives. Mol. Microbiol. 56:10491061.   15853889 
Zhou, D., Ren, J., Ryan, T., Higgins, N.P., and Townes, T. (2004) Rapid tagging of endogenous mouse genes by recombineering and ES cell complementation of tetraploid blastocysts. Nucl. Acids Res. 32: 1-7.   15356288 
Deng, S., Stein, R.A., and Higgins, N.P. (2004) Transcription-induced barriers to supercoil diffusion in the Salmonella typhimurium chromosome. Proc. Natl. Acad. Sci. USA 101: 3398-3403.   14993611 
Manna, D., Breier, A.M., and Higgins, N.P. (2004) Microarray analysis of transposition targets in Escherichia coli: The impact of transcription. Proc. Natl. Acad. Sci. USA 101: 9780-9785.   11344140 
Scheirer, K., and Higgins, N.P. (2001) Transcription induces a supercoil domain barrier in bacteriophage Mu. Biochimie 83: 155-159.   11278064 
Manna, D., and Higgins, N.P. (1999) Phage Mu transposition immunity reflects supercoil domain structure of the chromosome. Mol. Microbiol. 32: 595-606.   10320581 
Higgins, N.P., and Vologodskii, A. (2004) Topological behavior of plasmid DNA. In Plasmid Biology. Phillips, G. and Funnell, B. (eds). Washington D.C.: ASM Press, pp. 181-201.    
Higgins, N.P., Deng, S., Pang, Z., Stein, R., Champion, K., and Manna, D. (2005) Domain behavior and supercoil dynamics in bacterial chromosomes. In The Bacterial Chromosome. Higgins, N.P. (ed). Washington, D.C.: ASM Press, pp. 133-153.    
Higgins, N.P. (2005) The Bacterial Chromosome. Washington, D.C.: ASM Press.   
 

Keywords
Topoisomerases, Transposition, Site-specific Recombination, Genetics