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Belinda Pinto


belinda.pinto@gmail.com
Mentor: Pamela Geyer, Ph.D.
Lab Phone: 335-7967

Understanding the role of nuclear lamina proteins in nuclear organization and gene regulation

Understanding the role of nuclear lamina proteins in nuclear organization and gene regulation using Drosophila as a model

The integrity and organization of the nucleus depends upon the nuclear lamina, a protein network underlying the inner nuclear membrane. Lamina components include the intermediate filaments called lamins, as well as the LEM domain proteins, named for LAP2, emerin and MAN1. The LEM domain associates with a small, double stranded DNA binding protein called Barrier-to-autointegration factor (BAF) to establish a bridge between the nuclear envelope and interphase chromosomes. LEM domain proteins play a central role in nuclear lamina function; mutations in genes encoding these proteins cause a spectrum of human diseases that include cardiomyopathy, muscular dystrophy and bone density disorders. Mechanisms of lamina pathogenesis are unclear, as LEM domain proteins are globally expressed, yet phenotypic defects are tissue-restricted. To gain insights into these processes, we are isolating and characterizing mutations in the five Drosophila genes encoding LEM domain proteins. dMAN1 encodes the homologue of vertebrate MAN1 and LEM2. Mutations in this gene reduce viability and cause age-enhanced, tissue-specific phenotypes, including wing patterning and positioning defects, male sterility, reduced female fertility, aberrant climbing and flightlessness. These mutant phenotypes are rescued by expression of full-length dMAN1; the GAL4-UAS system is being used to define tissue-specific requirements for rescue. otefin encodes one of the two homologues of vertebrate emerin. Mutations in this gene reduce viability and cause female sterility. The absence of dMAN1 or Otefin does not appear to block cell division, as many tissues of appropriate size are formed. dMAN1 and otefin double mutants show more severe phenotypes than either single mutant. Taken together, our data imply that LEM domain proteins make unique and overlapping contributions to the lamina during tissue development.

Publications:

Pinto BS, Wilmington SR, Hornick EE, Wallrath LL, Geyer PK. Tissue-specific defects are caused by loss of the Drosophila MAN1 LEM domain protein. Genetics. 2008 Sep;180(1):133-45. Epub 2008 Aug 24. PMCID: PMC2535669 PMID: 18723885

Abstracts

Pinto, B.S., Wilmington, S.R., Wallrath, L.L. and Geyer, P.K. LEM Domain Proteins of the Nuclear Lamina make Unique and Overlapping Contributions to Drosophila Development. 67th Annual Meeting fo the Society of Developmental Biology, 2008.

Pinto, B.S., Wilmington, S.R., Wallrath, L.L. and Geyer, P.K. Understanding the Contributions of the LEM Domain Family of Nuclear Lamina Proteins to Drosophila Development. 47th Annual Midwest Developmental Biology Meeting, 2008.

Pinto, B.S., Wilmington, S.R., Wallrath, L.L. and Geyer, P.K. Tissue-specific Contributions of the Drosophila LEM Domain Protein dMAN1 in the Nuclear Lamina. 49th Annual Drosophila Research Conference, 2008.

Pinto, B.S., Wilmington, S.R., Hornick, E.E.L., Wallrath, L.L. and Geyer, P.K.Genetic analyses reveal tissue-specific contributions of the Drosophila LEM domain proteins in the nuclear lamina. 47th Annual ASCB Meeting, 2007.

Pinto, B.S., Wilmington, S.R., Wallrath, L.L. and Geyer, P.K. Using Drosophila as a model to understand human laminopathies: A study of dMAN1. 48th Annual Drosophila Conference, 2007.

Pinto, B.S., Wilmington, S.R., Wallrath, L.L. and Geyer, P.K. Using Drosophila as a model to understand human laminopathies: A study of dMAN1. Midwest Drosophila Conference, 2006.

Pinto, B.S., Wilmington, S.R., Schulze, S.R., Wallrath, L.L. and Geyer, P.K. A Study of LEM domain proteins in Drosophila: Characterization of the putative MAN1 homologue. 47th Annual Drosophila Research Conference, 2006.

Pinto, B.S., Wilmington, S.R., Yazgan, O., McDonough, C. W., Nalbant, D., Wallrath, L.L. and Geyer, P.K. A Study of LEM domain proteins in Drosophila: Characterization of the putative MAN1 homologue. ASCB Summer Meeting, Nuclear Architecture and Disease, 2005.



Honors and Awards

  • 47th Annual Midwest Develpmental Biology Research Conference, Iowa City, IA - 1st place, oral presen