Research Projects

Understanding the biochemical pathways essential for parasite growth and survival can help develop novel therapeutics. The aspartate pathway, found in plants and most bacterial strains, produces multiple amino acids like lysine, threonine, methionine, and isoleucine. It is essential to plants, fungi, and bacteria but absent in mammals. The enzyme homoserine dehydrogenase (HsD) functions in the third step of the aspartate pathway, reducing L-aspartate-β-semialdehyde to L-homoserine with NAD(P)H as cofactor or the oxidation of L-Homoserine using NAD(P)+ as cofactors. HsD crystal structures show it as a dimer containing nucleotide-binding, dimerization, and substrate-binding regions. It is monofunctional and homodimer, present in fungi, archaea, and gram-positive bacteria. The amnio acid threonine (Thr) is known to be crucial for the survival of trypanosomes in the bloodstream and a major source of acetyl coenzyme A for lipid biosynthesis. Deletion of the HsD gene in Candia albicans caused translational arrest and reduced cell adhesion. It is vital to survival in several other pathogens, such as Malassezia pachydermatis. The CRIsPR-Cas9 system can facilitate gene editing of Homoserine dehydrogenase, which is more efficient than homologous recombination used for genetic manipulation in Leishmania.