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Indiana University Bloomington

Department of Biology

Faculty & Research

Faculty Profile

Nicholas Sokol

Photo of Nicholas Sokol
Research Images
Research photo by Nicholas Sokol

A let-7-Complex transcriptional reporter is expressed in the nervous system of a newly hatched male fly. The muscle system is shown in purple and the let-7-Complex transcriptional reporter is shown in green. The asterisk indicates the location of the ventral nerve cord.

Research photo by Nicholas Sokol

Eye assay used to identify let-7-Complex target genes. Panel A depicts a fly carrying a normal copy of the eye pigmentation gene, white. Panel B depicts a fly carrying a copy of white that has been fused to the 3’UTR of a predicted let-7-Complex target gene. The reduction of eye pigment indicates that the 3’UTR represses gene expression. Panel C depicts a fly carrying the same white gene as in Panel B, except that in some eye cells let-7-Complex has been removed.  The derepression of eye pigmentation confirms that let-7-Complex microRNAs regulate gene expression via the target 3’UTR.

Assistant Professor of Biology
Contact Information
By telephone: 812-856-6812/6-4914(lab)
JH A504/JH A502A(lab)

FlyIU

Program
Genome, Cell & Developmental Biology
Research Areas
  • Behavior
  • Developmental Mechanisms and Regulation in Eukaryotic Systems
  • Eukaryotic Cell Biology, Cytoskeleton and Signaling
Education

Ph.D., Yale University, 2001
Postdoctoral Fellow, Dartmouth Medical School, 2001-2008

Awards

NIH-NIMH Biobehavioral Research Award for Innovative New Scientists (BRAINS), 2009

Research Description

MicroRNAs are a recently discovered class of small RNAs that regulate the expression of target genes. Some microRNAs have been highly conserved across millions of years of animal evolution, suggesting that their regulation of particular target genes plays an essential role in animal development and/or function. Yet, for many of these conserved microRNAs, their relevant gene targets as well as their developmental function are not known. We use the fruitfly Drosophila melanogaster to identify the molecular and cellular roles that evolutionarily conserved microRNAs play in the formation and function of complex organisms.

Our current interest is the function of a single gene, let-7-Complex, which encodes three different and highly conserved microRNAs (mir-100, let-7 and miR-125). Flies in which the let-7-Complex gene has been disrupted proceed through development and emerge as normal looking adults. However, these animals are defective in many adult behaviors (flight, locomotion, fertility, egg-laying, etc). We have found that a let-7-Complex transcriptional reporter is expressed throughout the nervous system during metamorphosis (see Figure 1). Therefore, we hypothesize that let-7-Complex microRNAs function in the profound remodeling of the nervous system that occurs during the larval to adult transition. We are taking the following steps to further characterize the function of the let-7-Complex gene.

  1. Analyze let-7-Complex mutant phenotypes. We are currently applying developmental neurobiology approaches to identify the particular neurons in which let-7-Complex microRNAs are expressed as well as characterize the cellular defects caused by their removal. We ultimately hope to connect particular let-7-Complex neuronal circuits to the behaviors affected but their removal.

  2. Characterize let-7-Complex target genes. Using an assay (see Figure 2) that we developed, we identified three target genes that let-7-Complex microRNAs regulate. We are currently studying where, when and why these three target genes need to be regulated by let-7-Complex microRNAs.

  3. Identify genes that regulate let-7-Complex expression and activity. In the eye assay presented in Figure 2, eye color provides a very clear indicator of let-7-Complex activity. This assay can therefore be used to identify genes that regulate let-7-Complex, which can range from transcription factors that specifically activate let-7-Complex expression to microRNA co-factors that regulate microRNA function more generally. We are conducting large-scale genetic screens to identify such genes.

Select Publications
Chawla, G, and Sokol, NS. Adar mediates differential expression of polycistronic microRNAs (Under review).
Luhur, A., Chawla, G., Wu, Y., Li, J., and Sokol, NS. A Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proceedings of the National Acadamy of Sciences (2014) doi:10.1073/pnas.1318445111
Luhur, A., Chawla, G., and Sokol, NS. MicroRNAs as components of systemic signaling pathways in Drosophila. Current Topics in Developmental Biology (2013) 105:97-123
Sokol NS. The role of microRNAs in muscle development. Current Topics in Developmental Biology (2012) 99: 59-78.    [article]
Sokol NS. Small temporal RNAs in animal development. Current Opinions in Genetics and Development (2012) May 9. [Epub ahead of print]  [article]
Wu, Y., Chen, C., Mercer, A., and Sokol NS. let-7-Complex microRNAs regulate the temporal identity of Drosophila mushroom body neurons via chinmo. Developmental Cell (2012) 23: 202-209.  [article]

Chawla G and Sokol NS. Hormonal activation of let-7-C microRNAs via EcR is required for adult Drosophila melanogaster morphology and function. Development (2012) 139:1788-1797.  [article]

Chawla G and Sokol NS. MicroRNAs in Drosophila Development. International Review of Cell and Molecular Biology (2011) 268: 1-65.  [article]
Gehrke S, Imai Y, Sokol NS, Lu B. Pathogenic LRKK2 negatively regulates microRNA-mediated translational repression. Nature (2010) 466: 637-31.  [article]
Sokol NS, Xu P, Jan Y-N, Ambros, V. Drosophila let-7 microRNA is required for remodeling of the neruomusculature during metamorphosis. Genes and Development (2008) 22: 1591-6.

Featured in:

  • Frasch M. A matter of timing: microRNA-controlled temporal identities in worms and flies. Genes and Development (2008) 22: 1572-6.
 [article]
Sokol NS, Identification, detection, and functional analysis of Drosophila microRNAs. Methods in Molecular Biology (2008) 420: 319-34  [article]
Sokol NS, Ambros V. Mesodermally expressed Drosophila microRNA-1 is regulated by Twist and is required in muscles during larval growth. Genes and Development (2005) 19: 2343-2354.

Featured in:

  • Nguyen H, Frasch M. MicroRNAs in muscle differentiation: lesson from Drosophila and beyond. Current Opinions in Genetics and Development (2006) 16:533-539. [cover]
  • Taylor, M. Developmental Biology: micromanaging muscle growth. Current Biology (2006) 16:R20-R23.
  • Brennecke J, Stark A and Cohen S. Not miR-ly muscular: microRNAs and muscle development. Genes and Development (2005) 19:2261-2265.

   [article]

Sempere LF**, Sokol NS**, Dubrovsky EB**, Berger EM, Ambros V.  Temporal regulation of microRNA expression in Drosophila melanogaster mediated by hormonal signals and broad-Complex gene activity. Developmental Biology (2003) 259:9-18. ** co-first authors.  [article]

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