Welcome to the labs of Drs. Kris Gunsalus and Fabio Piano at NYU New York City and NYU Abu Dhabi.
We study the genetic and evolutionary mechanisms underlying early embryonic development.
Genetic Interaction Networks in Development Post-transcriptional Regulation Dynamics of Cell Biology in the Early Embryo Evolution of Early Development and Reproductive Modes Chemical Genomics

Genetic Interaction Networks in Development

An organism’s fitness is determined by the coordinated action of gene networks. While some heritable diseases arise from mutations in individual genes, most arise from genetic interactions between multiple loci. We are using the nematode C. elegans to investigate how genes interact with each other to influence early development in this simple animal model system. Comprehensive gene knock-down studies have revealed that only around 15% of genes are essential on their own, whereas over half of annotated protein-coding genes are expressed in any individual cell. Therefore, we are particularly interested in learning about how non-essential genes contribute to essential developmental processes.
To study the architecture of genetic interactions in early development, we have developed a high-throughput (HTP) approach that combines genetically sensitized strains with RNAi to identify genetic modifiers of essential genes (Cipriani and Piano, 2011). So far, we have performed genome-wide screens for enhancers and suppressors of 24 temperature-sensitive alleles of genes with essential roles in the early embryo. Our HTP screening platform is aided by an image analysis algorithm we have developed called DevStaR, which uses computer vision and machine learning to quantify the survival rates of progeny in mixed populations of animals (White et al., 2013).
These studies are revealing how the embryo balances different competing demands, such as the generation of energy vs. the production of materials required during the rapid cell divisions that take place early in development.

Post-transcriptional Regulation

The spatiotemporal activity of genes and their products is regulated at many levels: transcription, translation, localization, and stability. Post-transcriptional regulation of mRNAs is mediated by numerous trans-acting factors, including microRNAs and many different kinds of RNA-binding proteins (RBPs). Many of these factors recognize cis-regulatory elements in 3’ untranslated regions (3’UTRs) of transcripts.
We are using molecular genetic and genomic approaches to study post-transcriptional regulation in C. elegans development. We also perform 3D structural modeling of miRISC and RBP complexes bound to RNA in order to identify energetic and structural constraints that govern how trans-interacting factors recognize and bind their cognate targets, and how RBPs may work together to regulate mRNA activity.

Dynamics of Cell Biology in the Early Embryo

Animal development unfolds through the coordination of complex cellular processes involving a multitude of molecular components. We are working toward a global understanding of the dynamic organization of the single-celled zygote by generating a dynamic subcellular localization map of proteins in the early embryo.
We have generated 100 GFP-tagged proteins and described their in vivo localization patterns in the single-celled zygote over time. We have generated dynamic association networks from these data, which we are using to develop and test hypotheses about protein function using molecular epistatic and biochemical techniques.

Evolution of Early Development and Reproductive Modes

There is much more to early embryogenesis in nematodes than just what we can discover by studying C. elegans. Nematodes display a great variety in cellular events in the early embryo, particularly in the timing and orientation of the first cell divisions. Moreover, evolutionary changes in reproductive modes are common in this phylum, where every type of reproductive mode is represented: gonochoristic (male-female), hermaphroditic (self-fertilizing), and parthenogenic (asexual). We study the evolutionary mechanisms underlying early embryonic development, as well as reproductive modes, using a combination of microscopy, functional genomics, and molecular genetic approaches in nematodes related to C. elegans. We are currently focusing our attention on a particularly intriguing group of nematodes that sometimes show a different pattern of early cell divisions: Protorhabditis. We have sequenced and annotated the genome of one asexually reproducing species in this group, and we have found that it has a very unusual genome architecture that provides clues regarding the possible mechanisms by which parthenogenesis may evolve from a male-female reproductive system.

nematode phylogeny tree

Chemical Genomics

In our lab in Abu Dhabi, we have developed a high-throughput screening platform for whole-organism and cell-based assays. We are using this HTP platform to investigate chemical genetic interactions using small molecule libraries or natural products. Some examples include:

  • Anthelmintics: Parasitic nematodes infect over one billion people and cause extensive damage to livestock and crop plants say year. We are using the free-living, non-infectious nematodes C. elegans and P. pacificus to screen for novel compounds with therapeutic potential as broad-spectrum nematocidal agents.
  • High-content screening (HCS) in mammalian cells: We have developed a panel of cellular markers that report on a variety of cellular structures and pathway activities, which we are using to identify and characterize cell biological phenotypes elicited by bioactive compounds. Novel bioactives may serve as lead compounds for therapeutic applications such as cancer treatments, or provide new biomarkers that can be used as tools for basic research into molecular mechanisms of cell biological processes.
  • Natural products discovery: We are analyzing samples from coastal habitats in the Abu Dhabi region to identify novel bioactive compounds produced by microorganisms isolated from these unique ecological environments.