A research team led by University of California, Riverside has generated the first such 3D architecture during the progression of the life cycle of a parasite.
According to the World Health Organisation, an estimated 207 million people were infected with malaria in 2012, leading to 627,000 deaths, researchers said.
"Understanding the spatial organisation of chromosomes is essential to comprehend the regulation of gene expression in any eukaryotic cell," said Karine Le Roch, an associate professor of cell biology and neuroscience, who led the study.
Her research team also found that those genes that need to be highly expressed in the malaria parasite — for example, genes involved in translation — tend to cluster in the same area of the cell nucleus.
On the other hand genes that need to be tightly repressed — for example, those involved in virulence — are found elsewhere in the 3D structure in a "repression center."
Virulence genes in the malaria parasite are a large family of genes that are responsible for the parasite's survival inside humans, researchers said.
Le Roch's team found that these genes, all organized into one repression centre in a distinct area in the nucleus, seem to drive the full genome organization of the parasite.
"We successfully mapped all physical interactions between genetic elements in the parasite nucleus," Le Roch said.
Scientists used a 'chromosome conformation capture method,' followed by high throughput sequencing technology — a recently developed methodology to analyze the organisation of chromosomes in the natural state of the cell.
They then used the maps of all physical interactions to generate a 3D model of the genome for each stage of the parasite life cycle analyzed.
To understand the biology of an organizm or any cell type, scientists need to understand not only the information encoded in the genome sequence but also how the sequence is compacted and physically organised in each cell/tissue, and how changes in the 3D genome architecture can play a critical role in regulating gene expression, chromosome morphogenesis and genome stability.
"If we understand how the malaria parasite genome is organized in the nucleus and which components control this organization, we may be able to disrupt this architecture and disrupt, too, the parasite development," Le Roch said.
"We know that the genome architecture is critical in regulating gene expression and, more important, in regulating genes that are critical for parasite virulence. Now we can more carefully search for components or drugs that can disrupt this organisation, helping in the identification of new anti-malaria strategies," said Le Roch.
The study appears in the journal Genome Research.
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