Himanshu Khandelia

My research evolves around computer simulations of complex biological assemblies, with special focus on biological membranes and membrane associated biological processes. The ultimate objective is to obtain fundamental scientific insight into both the assembly and evolution of complex biomolecular structures through interactions and modification of their environment; and into the functioning of isolated biomolecular machines. The goal of the investigations will also be to examine the fundamental molecular basis of diseased states resulting from a perturbation of these interactions, thus motivating biotechnological applications and the rational development of therapeutic remedies and drugs. An important feature of this research is a close interface with experiments, wherein experimental data will motivate simulations, which in turn will drive new analytical measurements. With this goal, several collaborations with leading experimental groups have been established. Representative Examples: The following are some examples of projects. All of them address fundamental scientific problems, and also have biotechnological and medical applications. My most recent work involves the discovery of multiple ion pathways in trans- membrane ion pumps, a proposal that is likely to forever change the way biology looks at ion transport (Nature, 2010, DOI: 10.1038/nature09309). In another project, we have shown for the first time, that triglyceride droplets can be stable within lipid bilayers, this has implications for lipid droplet biogenesis and the mobile lipid signal in cancer cell membranes (PLoS One, 2010, DOI: 10.1371/journal.pone.0012811). We showed how oxidized phospholipids -which are now known be in involved in the genesis of several diseases- can significantly alter the biochemical andbiophysicalpropertiesoflipidmembranes(Biophys.J.,2009,DOI: DOI:10.1016/j.bpj.2009.01.007). In recent collaborative work with the Danish Cancer Society and the University of Helsinki Medical School, we showed for the first time that lipid secondary messengers could be targeted for anticancer therapy (JACS, 2008, DOI: 10.1021/ja800516w). The seminal nature of the work attracted lot of press coverage in the scientific community. In yet another set of projects, I am investigating the effect of medicinal plant extracts on biological membranes and proteins residing therein. These representative examples illustrate the significant role of molecular simulations in the investigation of the molecular basis of diseased states, and consequent importance in realm of fundamental and health sciences research.