Novel Applications of Genomic Markers for Clinical and Phylogenomic Studies
Genomes are the ultimate repositories of genetic information present in biological organisms making them some of the most exciting and insightful targets for microbial research. Recent advances in genome sequencing technology are making an extraordinary amount of information available that has the potential to provide novel insights into the physiology, biochemistry, and evolution of different organisms.
My group probes this wealth of genetic information using innovative in silico approaches spanning comparative genomics, protein modelling, phylogenetics, molecular simulations, protein interaction modelling, and protein network analysis. The main focus of our current research is to use sequence information from different genomes to identify unique molecular characteristics, such as signature proteins or conserved indels (i.e. inserts or deletions) in protein sequences which serve as distinctive characteristics of different groups of organisms. We have developed a highly-efficient pipeline for the datamining of these novel molecular signatures from genome sequences. These novel molecular characteristics serve as powerful tools for understanding several different aspects of organisms.
These include (i) Understanding the evolutionary relationships among different prokaryotic and eukaryotic organisms to develop a more reliable classification scheme for organisms based on molecular sequence data; (ii) Understanding the cellular functions of these lineage (or organism)-specific molecular signatures through genetic, biochemical and bioinformatics studies; (iii) Development of novel diagnostic methods for identifying distinct groups of organisms based upon such identified molecular signatures; and (iv) Applications of the identified conserved indels found in essential proteins as potential drug targets for developing new classes of therapeutics specifically targeting particular groups of organisms.
One example of the work we do is provided by our recent study on mycobacterial species. Our comprehensive analyses of genome sequences from mycobacterial species have led to the division of the genus Mycobacterium into five different genera. Due to our work, the genus name Mycobacterium is now limited to a small group of mycobacterial species, containing all major human and animal pathogenic species, which are clearly distinguishable from all others by numerous molecular signatures. The remainder of the mycobacterial species, which are non-pathogenic or are of lesser clinical significance, are now placed into four new genera and will be known by the names Mycolicibacterium, Mycolicibacter, Mycolicibacillus and Mycobacteroides. With the explicit division of mycobacterial species into these distinct groups, attention can now be focused on the unique genetic and molecular characteristics that are specific for the clinically important group of mycobacteria paving the way for important developments in this field.
The Gupta Lab has a strong publication record. The collaborative and bioinformatics nature of our work has resulted in many of the PhD students from the lab being involved in over a dozen published projects over the course of their graduate career. Additionally, nearly half of the undergraduate students in the lab have been able to complete research projects leading to authorships in publications. Lastly, our work using genomic approaches is not limited to microorganisms. We are also actively engaged in identifying molecular signatures that are specific for different groups of eukaryotic organisms (e.g. plasmodium, nematodes, pathogenic fungi, primates, etc.) providing important and interesting means for different types of studies.