A poorly studied malaria protein could serve as a key drug target to help combat the growing problem of resistance.

Transcript

A poorly studied malaria protein – Plasmodium falciparum histone deacetylase 1 – could serve as a key drug target to help combat the growing problem of resistance. The protein helps regulate the ‘intraerythrocytic’ stage of the parasite: a 48-hour cycle in which the parasite invades, replicates, and bursts free from red blood cells, causing disease symptoms. By making this protein fluorescent, researchers found that it is associated with a range of major biological functions that help the parasite progress through this stage, particularly during the ‘trophozoite’ (or mature) stage. When PfHDAC1 was overexpressed, the number of malaria parasites increased – along with the expression of other genes responsible for parasite development. Dihydroartemisinin—a key antimalarial drug—ordinarily interferes with these biological processes, but overexpression of the protein leads to reduced sensitivity and resistance. This research reveals more about the parasite lifecycle in the human body and suggests a new drug target against it.

Source

PfHDAC1 is an essential regulator of P. falciparum asexual proliferation and host cell invasion genes with a dynamic genomic occupancy responsive to artemisinin stress

About The Podcast

The Johns Hopkins Malaria Minute podcast is produced by the Johns Hopkins Malaria Research Institute to highlight impactful malaria research and to share it with the global community.

How sickle cell disease can be a blessing and a curse. And why we need equity in genomic research and to diversify the genomes we sequence.

With Ambroise Wonkam (Johns Hopkins University).

The Johns Hopkins Malaria Minute is produced by the Johns Hopkins Malaria Research Institute to highlight impactful malaria research and to share it with the global community.

Malaria is one of humanity’s oldest diseases – and one with which we have evolved.

Transcript

Malaria is one of humanity’s oldest diseases – and one with which we have evolved. Over time, it’s put selective pressure on our genome to respond better to its infection. Sickle cell disease is one example. It causes a defect in hemoglobin – transforming red blood cells into a banana or sickle shape – reducing the amount of oxygen transported to the body’s cells. The mutation has been around for more than 20,000 years – and is thought to originate near present-day Cameroon. But in one of the many evolutionary twists, under the right conditions, sickle cell disease can protect humans from malaria, because it makes it harder for malaria parasites to infect red blood cells. Possessing one copy is an asset, providing resistance to severe malaria, but if two copies of the mutation appear, it is a liability, leading to premature death. The evolutionary relationship between malaria endemicity and sickle cell disease is evident geographically. This complex, genetic legacy is the focus of an upcoming talk by Ambroise Wonkam at the Johns Hopkins Malaria Research Institute’s World Malaria Day symposium on April 25th.

Source

Evolutionary history of sickle-cell mutation: implications for global genetic medicine

About The Podcast

The Johns Hopkins Malaria Minute podcast is produced by the Johns Hopkins Malaria Research Institute to highlight impactful malaria research and to share it with the global community.