The Varadarajan Laboratory

The laboratory seeks to understand determinants of protein structure and stability. We use saturation and saturation suppressor mutagenesis coupled to deep sequencing to guide protein structure prediction, probe protein:ligand interfaces and understand in vivo determinants of protein stability.

In addition to basic research on protein stability and folding, the lab is interested in the design of proteins for specific biological applications. Over the past several years a significant part of our effort is devoted to design HIV-1 envelope protein (Env) derived immunogens to elicit broadly neutralizing antibodies. We have designed novel, trimeric, cyclically permuted versions of gp120 and recently demonstrated in collaborative studies that these elicited broadly neutralizing sera in guinea pigs and broadly protective antibodies in rabbits and macaques. We have also designed immunogens that elicit protective antibodies against influenza virus, another global health threat, and were one of the first to design an immunogen consisting of the conserved stem region of the viral surface protein HA. The immunogen was shown to confer heterologous protection against pathogenic viral challenge in mice. More recently we describe the design of a thermo-tolerant bacterially expressed stem fragment that elicits broadly reactive antibodies and protects against heterologous challenge from both group 1 and group 2 influenza viruses. Very recently, we have initiated work on immunogens derived from the spike glycoprotein of SARS-CoV-2, the causative agent of the COVID-19 pandemic. These are being tested in small animals, primarily in collaboration with the Bengaluru based startup, Mynvax.