Chemical and Functional Genomics

Chemical and Functional Genomics

Principal investigators: Kristin Gunsalus, Fabio Piano

This program addresses key areas of human health using a combination of experimental and bioinformatic approaches. We have developed a high-throughput screening platform to identify and characterize novel bioactive molecules and their molecular targets using whole organism and cell-based assays. Our current focus is in two discovery areas aimed at developing novel potential therapeutic strategies for parasitic nematode infections and other diseases like cancer, using small molecule libraries and natural products derived from microbes that populate different ecological niches in the region. hela-golgi-stained

High-content phenotypic profiling is a powerful way to identify novel bioactive molecules and to classify their mode of action based on similarity with compounds of known effect. We are developing multiple mammalian cell lines with panels of molecular markers that report on various cellular compartments, structures, and signaling pathways, which we use to measure changes in cellular morphology and activity using automated high-content image analysis tools. In addition to unbiased screening, we are also applying rational design to target specific interactions within cells and determine whether these can form a basis for development of new combinatorial therapeutic strategies.

Identifying molecules that mediate specific effects in whole organisms is still one of the great challenges in drug discovery. Unfortunately, the vast majority of lead compounds identified with standard in vitro approaches fail to be useful in vivo. The nematode C. elegans is a premier candidate to pioneer whole-organism chemical systems biology: one of the most advanced models for genetics, functional genomics, and systems biology, it was the first animal to have its genome completely sequenced and is the only one for which the entire developmental cellular lineage is completely known. Nearly 3/4 of known human disease genes are conserved in C. elegans, which has been used to decipher molecular mechanisms relevant to human development, aging, behavior, cancer, diabetes, and other diseases.

C. elegans is not only a good model for human disease, but holds promise for developing compounds that specifically inhibit the growth or reproduction of nematode worms (anthelmintics). Parasitic nematodes infect an estimated 2 billion people worldwide and cause damage to domestic livestock and crops, resulting in severe economic losses each year. Resistance is rising around the world to the handful of currently available drugs to treat these diseases, which have been in use for decades. Our aim is to discover novel broad-spectrum anthelmintics that target parasitic nematodes. Our approach uses related free-living, non-pathogenic species to screen for candidate bioactive compounds, which will then be tested for toxicity in parasitic and host models in collaboration with other research groups.

hela-nucleus-actin-stainedSeveral of our ongoing projects involve collaborations with other research groups at NYUAD (Shady Amin, Piergiorgio Percipalle), NYU (Bobby Arora), and other institutions in the region (e.g. Christian Voolstra, KAUST) and around the globe. Our collaborative projects focus on a variety of different biological questions that are all facilitated by our high-throughput and/or high-content screening systems.

Take a look at our awesome robot in action!

pluto.bio.nyu.edu/wordpress/HTS_Video_2015.mov

Researchers and Staff:

Glenn Butterfoss: Senior Research Scientist
Giselle Cipriani: Senior Research Scientist (NYUNY and NYUAD)
Hala Fahs: Senior Research Scientist
Suma Gopinadhan: Research Associate
Rawan Kalloush: Research Assistant
Stephan Kremb: Research Scientist
Yanthe Pearson: Research Scientist
Fathima Shaffra Mohammed: Research Associate

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