A class of extremising sphere-valued maps with inherent maximal tori symmetries in SO(n)

In this paper we consider an energy functional depending on the norm of the gradient and seek to extremise it over an admissible class of Sobolev maps defined on an annulus and taking values on the unit sphere whilst satisfying suitable boundary conditions. We establish the existence of an infinite family of solutions with certain symmetries to the associated nonlinear Euler-Lagrange system in even dimensions and discuss the stability of such extremisers by way of examining the positivity of the second variation of the energy at these solutions

Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach

Malaria is an infectious disease caused by parasites of the genus Plasmodium, which leads to approximately one million deaths per annum worldwide. Chemical validation of new antimalarial targets is urgently required in view of rising resistance to current drugs. One such putative target is the enzyme N-myristoyltransferase, which catalyses the attachment of the fatty acid myristate to protein substrates (N-myristoylation). Here, we report an integrated chemical biology approach to explore protein myristoylation in the major human parasite P. falciparum, combining chemical proteomic tools for identification of the myristoylated and glycosylphosphatidylinositol-anchored proteome with selective small-molecule N-myristoyltransferase inhibitors. We demonstrate that N-myristoyltransferase is an essential and chemically tractable target in malaria parasites both in vitro and in vivo, and show that selective inhibition of N-myristoylation leads to catastrophic and irreversible failure to assemble the inner membrane complex, a critical subcellular organelle in the parasite life cycle. Our studies provide the basis for the development of new antimalarials targeting N-myristoyltransferase