Maureen M. Barr, Ph.D.

Assistant Professor
Pharmaceutical Sciences Division

mmbarr@pharmacy.wisc.edu

Trainer in the Following Programs:

  • Molecular and Cellular Pharmacology Program
  • Celular and Molecular Biology
  • Genetics
  • Molecular Biosciences
  • Neuroscience
  • Pharmaceutical Sciences

Honors and Awards:

  • Howard Hughes Medical Institute Postdoctoral Fellow

Molecular basis of sensory transduction:

The goal of my research is to understand the mechanisms by which invertebrate nervous systems process sensory information. In the nematode Caenorhabditis elegans, the simple nervous system, powerful genetics, and fully sequenced genome enables study of signal transduction pathways at the behavioral, cellular, genetic, molecular, and biochemical levels. The "worm" has proven extremely useful for defining pathways of gene action and identification of new proteins involved in a particular pathway. We are using C. elegans as a model system for studying chemosensation, mechanosensation, synaptic transmission, intraflagellar transport (IFT), and two human genetic disorders: autosomal dominant and recessive polycystic kidney diseases (ADPKD and ARPKD).

ADPKD: Defects in a sensory channel complex?

ADPKD strikes 1 in 1000 individuals, often resulting in end-stage renal failure. Mutations in either PKD1 or PKD2 account for 95% of all cases. Recently, polycystin-1 and polycystin-2 (encoded by PKD1 and PKD2, respectively) have been demonstrated to assemble to form a cation channel in vitro. We have identified and characterized the worm counterparts of PKD1 and PKD2, lov-1 and pkd-2, respectively. Surprisingly, these genes are necessary for C. elegans males to sense their mates during sex; we think that the roles of the proteins within a cell are conserved, but that the overall affect on the organism (worm behavior vs. human kidney development/function) is likely very different. We have found that LOV-1 and PKD-2 act non-redundantly in the same pathway, localize to the ciliated sensory endings of male-specific chemosensory neurons, and are not required for ciliogenesis. We will continue to use C. elegans to study the function(s) of PKD1 and PKD2 and to identify new genes that act in the ADPKD pathway.

Molecular mechanisms of sensation

To begin to unravel the molecular basis of sensory behaviors such as touch, taste, and smell, we will take advantage of the C. elegans completely sequenced genome using a functional genomics approach. The C. elegans male nervous system possesses multiple sensory neurons that are required for male mating behavior. To investigate the role of mechanosensation in mating, we are characterizing the touch receptor molecules, the DEG/ENaC (degenerin and epithelial sodium channel) ion channel gene family. Similarly, we are also determining the expression patterns and functions of male-enriched neuronal genes that encode signal transduction molecules such as G-protein coupled receptors, channels, transporters, neurotransmitters, and neuropeptides. Our studies may shed light on the basic molecular mechanisms an animal uses to sense, process, and respond to environmental stimuli.

Figure Legend: Polycystin 1 (PC1) and polycystin 2 (PC2) family members all share a similar predicted transmembrane (tm) spanning domain architecture. PC1 and LOV-1 possess (i) a large extracellular domain that does not share sequence similiarity, (ii) a GPS (G-protein coupled receptor sequence) cleavage site, (iii) eleven tm domains, (iv) an intracellular PLAT domain between tm1 and tm2 (blue box), and (v) tm domains (red) that are homologous to PC2. PC2 and PKD-2 share features characteristic of a cation channel, namely, (i) 6 tm domains, (ii) a pore region between tm5 and tm6 and (iii) homology to TRP channels. PC2 members all possess a coiled-coil domain that may mediate protein-protein interactions.

Selected Recent Publications:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=search&term=barr%2Bmm

  • Bae YK, Qin H, Knobel KM, Hu J, Rosenbaum JL, and Barr MM. (2006). General and cell-type specific mechanisms target TRPP2/PKD-2 to cilia. Development. 133:3859-3870. PDF PMID 16943275

  • Hu J, Bae YK, Knobel KM, and Barr MM. (2006). Casein kinase II and calcineurin modulate TRPP function and ciliary localization. Mol Biol Cell. 17:2200-2211. PDF PMID 16481400

  • Qin H, Burnette DT, Bae YK, Forscher P, Barr MM, and Rosenbaum JL. (2005). Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane. Curr Biol. 15:1695-1699. PDF PMID 16169494

  • Jauregui AR and Barr MM. (2005). Functional characterization of the C. elegans nephro-cystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviors. Exp Cell Res. 305:333-342. PDF PMID 15817158

  • Peden EM and Barr MM. (2005). The KLP-6 kinesin is required for male mating behaviors and polycystin localization in Caenorhabditis elegans.  Curr Biol. 15:394-404. PDF PMID 15753033

  • Barr MM. (2005). Caenorhabditis elegans as a model to study renal development and disease: sexy cilia. J Am Soc Nephrol. 16:305-312. PDF PMID 15647338

  • Hu J and Barr MM. (2005). ATP-2 interacts with the PLAT domain of LOV-1 and is involved in Caenorhabditis elegans polycystin signaling. Mol Biol Cell. 16:458-469. PDF PMID 15563610

  • Wang J and Barr MM. (2005). RNA interference in C. elegans. Methods in Enzymology. 392:36-55. PMID 15644174

  • Barr MM. (2004). C. elegans as a Model of Renal Development and Disease. JASN. 16:305-312. Review.

  • Barr MM. (2003). Super Models. Physiol Genomics. 13:15-24. PDF PMID 12644630

  • Qin H, Rosenbaum JL, and Barr MM. (2001). An autosomal recessive polycystic kidney disease gene homolog is involved in intraflagellar transport in C. elegans ciliated sensory neurons. Curr Biol. 11:457-61. PDF PMID 11301258

  • Barr MM, DeModena J, Braun D, Nguyen CQ, Hall DH, and Sternberg PW. (2001). The Caenorhabditis elegans autosomal dominant polycystic kidney disease gene homologs lov-1 and pkd-2 act in the same pathway. Curr Biol. 11:1341-1346. PDF PMID 11553327

  • Barr MM and Sternberg PW. (1999). A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Nature. 401:386-9. PDF PMID 10517638


Invited review:

  • Barr, M.M. Super models. Physiol. Genomics (2003) 13:15-24.

Book chapters in press:

  • Barr, M.M. and Wang, J. RNAi in C. elegans in RNA interference nuts and bolts (2003). Editor: David R. Engelke. Publisher: DNA Press.

  • Barr, M.M. and Hu. J. Molecular basis of behaviour in Nematode Behaviour (2003). Editor: Randy Gaughler. Publisher: CABI press.

Scientists in the Barr Lab:

Postdoctoral Fellows:

  • Dr. Karla M. Knobel
  • Dr. Jinghua Hu
  • Dr. Juan Wang

Graduate Students:

  • Young-Kyung Bae (Genetics)
  • Tiewen Liu (Genetics)
  • Andrew Jauregui (Genetics)

Research Specialist:

  • Douglas R. Braun

Undergraduates:

  • Julie A. Karl
  • Dave Saber
  • Sam Wittekind

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