I am a Systems Biologist and Bioinformaticist, focusing on the study of interactomes and interaction networks for understanding local and global relationship between gene products, and how such associations lead to complex, functional, biological systems. I use comparative genomics and sequence analysis tools to model interactomes, predict protein function and detect novel cellular systems.

The organisms I investigate include Plasmodium falciparum, a parasite that causes a severe form of malaria in humans, and is responsible for most of the nearly 2 million deaths worldwide due to the disease. Malaria, along with Tuberculosis and HIV/AIDS is ranked by the World Health Organization (WHO) as one of the top 3 killer diseases that threaten human health. Because of the absence of the disease from developed western countries, it has been traditionally ignored, until recently, when foundations like the one set up by Bill and Melinda Gates promised to pour large sums of money into research and programs for prevention and treatment.

Given the importance of the disease, the genome of P. falciparum was sequenced by a consortium of international investigators and made publicly available in 2002. The genome sequence encodes ~5000 proteins and reveals many oddities, including the fact that more than 60% of the gene products cannot be characterized using common methods of protein function assignment. Absence of functional information for such a large number of proteins precludes our understanding of the inner workings of the organism, concealing promising information that can be used to find drug targets or vaccine candidates.

The main focus of my investigation is to use computational tools to analyze the P. falciparum genome and generate networks of protein-protein interactions, so that functional information for uncharacterized genes or proteins can be obtained in a high-throughput manner. Recently, we developed a strategy that allows integration of functional genomics data from diverse experiments within a Bayesian framework, the results of which were published in the Genome Research journal (see Date & Stoeckert, 2006). Application of this method led to the reconstruction of a high-quality map of the P. falciparum interactome, which provides functional information for more than 2000 uncharacterized gene products. The information generated from this project is intended to serve as a starting point for experiments and assays that look at gene function in greater detail. Besides such data integration methods for understanding genome content, I am also developing methods aimed at finding patterns or motifs in large groups of proteins, which can be investigated for their functional roles using computational or experimental methods. An important aim is also to make such schemas and methods universal, so that they can be applied to genomes of higher eukaryotes like humans and mice. I am also modeling interactomes of Toxoplasma gondii and Cryptosporidium parvum, the respective causal organisms of Toxoplasmosis and Cryptosporidiasis in immuno-compromised patients.

A functional interaction network of P. falciparum (colored links represent life-cycle stages (see Date & Stoeckert, 2006)



Assigning function to unknown proteins using the 'guilt-by-association' principle. (see Date & Stoeckert, 2006)



Presence/absence of components of novel pathways discovered in Bacteria (see Date & Marcotte, 2003)