Nicholas Sokol

Nicholas Sokol

Associate Professor, Biology

  • nsokol@indiana.edu
  • (812) 856-6812
  • Jordan Hall A504
  • Office Hours
    M-F
    By Appointment Only

Education

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

About

Lab

Jordan Hall A502A
(812) 856-4914
Sokol Lab website

Awards

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

Research

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-Complexexpression to microRNA co-factors that regulate microRNA function more generally. We are conducting large-scale genetic screens to identify such genes.

Research areas

Developmental Mechanisms and Regulation in Eukaryotic Systems
Eukaryotic Cell Biology, Cytoskeleton, and Signaling

Publications

Luhur, A., Buddika, J., Ariyapala, I., Chen, S., and Sokol, NS. Opposing post-transcriptional control of InR by FMRP and LIN28 adjusts stem cell based tissue growth. Cell Reports.

Chawla, G., Childress, S., Deosthale, P., and Sokol, NS. A let-7-to-miR-125 microRNA switch regulates neuronal integrity and lifespan. PLoS Genetics (2016). 12(8): e1006247. doi: 10.137

Narbonne-Reveau, K., Lanet, E., Dillard, C., Foppolo, S., Chen, CH., Parrinello, H., Rialle., S., Sokol, NS., and Maurange, C. Neural stem cell-encoded temporal patterning delineates an early window of malignant susceptibility in Drosophila. eLIFE (2016) 14;5. pii: e13463. Doi: 10.7554

Chen, CH., Luhur, A., and Sokol, NS. Lin-28 promotes symmetric stem cell division and drives adaptive growth in the adult Drosophila intestine. Development (2015) 142(20): 3478-87. PMID 26487778.

Luhur, A., Chawla, G., Wu, Y., Li, J., and Sokol, NS. A Drosha-independent DGCR8/Pasha pathway regulates neuronal morphogenesis. Proceedings of the National Academy of Sciences (2014) 111:1421-6 (IF = 9.7)

See all publications
An adult Drosophila intestine. Cell nuclei are labeled in magenta, and progenitor cells are labeled in green. The adult Drosophila intestine is a model system for understanding the relationship between stem cell and tissue dynamics.

An adult Drosophila intestine. Cell nuclei are labeled in magenta, and progenitor cells are labeled in green. The adult Drosophila intestine is a model system for understanding the relationship between stem cell and tissue dynamics.

A close-up of two intestinal progenitor cells. Cell nuclei are labeled in blue. Two different RNA-binding proteins are labeled in green and red, respectively. The yellow spots are “stress granules,” hubs of RNA and RNA binding proteins that are located in stem cells and that highlight the importance of RNA pathways in stem cell biology.

A close-up of two intestinal progenitor cells. Cell nuclei are labeled in blue. Two different RNA-binding proteins are labeled in green and red, respectively. The yellow spots are “stress granules,” hubs of RNA and RNA binding proteins that are located in stem cells and that highlight the importance of RNA pathways in stem cell biology.

GFP specifically labels the intestinal progenitor cells (arrowhead) in an adult fly. The Sokol lab has invested in building genetic tools such as the one shown here. These tools are allowing the lab to perform largescale identification and analysis of the RNA-protein complexes present in progenitor cells.

GFP specifically labels the intestinal progenitor cells (arrowhead) in an adult fly. The Sokol lab has invested in building genetic tools such as the one shown here. These tools are allowing the lab to perform largescale identification and analysis of the RNA-protein complexes present in progenitor cells.

The central nervous system of a 3rd instar Drosophila larva. Two RNA-binding proteins, LIN28 and FMRP, are labeled in green and red respectively. The Sokol lab uses the developing nervous system to investigate the overlap in the regulatory RNA pathways that operate in a variety of stem cell populations.

The central nervous system of a 3rd instar Drosophila larva. Two RNA-binding proteins, LIN28 and FMRP, are labeled in green and red respectively. The Sokol lab uses the developing nervous system to investigate the overlap in the regulatory RNA pathways that operate in a variety of stem cell populations.

The central nervous system of an adult fly. The expression pattern of a microRNA cluster is labeled in green. Projects in the Sokol lab are focused on understanding the role of microRNA pathways in the formation and function of the adult nervous system.

The central nervous system of an adult fly. The expression pattern of a microRNA cluster is labeled in green. Projects in the Sokol lab are focused on understanding the role of microRNA pathways in the formation and function of the adult nervous system.