LINCing nuclear and cellular dynamics in malaria parasites

Malaria remains one of the deadliest infectious diseases on earth today, and despite tremendous efforts there is still no effective vaccine for this illness. The deadliest form of human malaria is caused by the protozoan parasite, Plasmodium falciparum, which annually infects millions of people worldwide. The malaria parasite has a complex life cycle alternating between anopheline mosquitoes and the human hosts, however, the only stages that cause malaria are those that proliferate in the human blood circulation. The reason why P. falciparum is such a successful and virulent parasite, is because of its ability undergo series of cellular divisions where, every 48 hours, one parasite replicate into ~30 daughter parasites. During its unique cellular division, the parasite must protect its genome integrity from human immune attack while tightly controlling mechanisms of gene expression that enables immune evasion. This biological complexity requires tight link between processes that happen in the parasite nucleus and those that occur in the cytoplasm. These two compartments are by the nuclear envelope. One of the major protein complexes that is known to function as a bridge between the nucleus and the cytoplasm is called the LINC complex. In higher eukaryotes it was shown to play important roles nuclear and cell division, gene expression, and the maintenance of genome integrity. There is evidence that components of the LINC complex in P. falciparum are important for parasite proliferation within human blood and that play a role in controlling virulence genes and repairing DNA damage. The rationale for the proposed study is that understanding the molecular mechanisms that enable the parasite to successfully proliferate within human blood will allow for the future discovery of new drugs that interrupt this process and thereby lessen the severity of this devastating disease or aid in the elimination of parasites from infected individuals.

Basic Science

Jan 2023

Israel
United States