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 works on viral vaccine design. We have previously designed HIV-1 envelope protein (Env) derived immunogens with the goal of eliciting broadly neutralizing antibodies. This included novel, trimeric, cyclically permuted versions of gp120. In recent collaborative studies, 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. During the COVID-19 pandemic, we developed various thermostable vaccine COVID-19 vaccine formulations derived from the Spike glycoprotein of SARS-CoV-2. In collaboration with the Bengaluru based startup, Mynvax, one of these formulations is being moved forward to clinical testing.