A parasite carried by billions of people worldwide often causes harmful infections during pregnancy, in immunocompromised individuals, and is the cause of a leading infectious blindness in South America. Once it enters the body, it can rapidly multiply, spreading from one cell to the next.
This single-celled organism, Toxoplasma gondii , belongs to the same group of microbes as the parasite that causes malaria and many other parasites of humans and animals. Cats are Toxoplasma ’s main host, but it can infect most warm-blooded mammals, including humans, who typically become infected through contact with cat feces or by consuming undercooked meat or contaminated produce.
The parasite’s ability to survive and spread inside a host depends on its capacity to precisely control which proteins it makes and when. Proteins are the molecular machinery that carry out all of the parasite’s functions, from invading and manipulating host cells to making new copies of the pathogen that spread to other cells and hosts.
This means that at different points in its life cycle, Toxoplasma must have different sets of proteins available in a tightly timed sequence, so it can quickly switch between growth, replication, and infection states.
Now, Whitehead Institute Member Sebastian Lourido and former graduate student Dominic Schwarz have uncovered new details about how Toxoplasma controls the timing of protein production, ensuring the right molecular tools are available exactly when they are needed.
Their work, published July 16 in Nature Communications , reveals that two protein complexes — groups of proteins that work together like molecular machines — manage this process. One complex promotes the production of proteins needed for the parasite’s current life stage. The other keeps instructions, or genes, for making certain proteins in a poised state — accessible but not yet active — so they are ready when the parasite shifts into a different stage or encounters new conditions.
“You can think of it almost like the parasite is going through its genome, reading some instructions now and placing bookmarks on others for later,” says Lourido, who is also an associate professor of biology at the Massachusetts Institute of Technology (MIT). “This allows the parasite to quickly make complex decisions and move between different stages of infection.”
Prior to this work, scientists had identified many of the genes that enable Toxoplasma to replicate, but much less was known about the molecular systems that control when and how those instructions were used to make the corresponding proteins. Understanding these systems could guide new ways to prevent and treat parasitic infections.
The “bookmarking” process depends on how DNA is packaged inside the parasite’s cells: long strands of DNA are wound around proteins like thread wrapped around a bobbin. Regions that are tightly wound up tend to keep protein-making instructions inaccessible, while more open regions make those instructions easier to read. The molecular machinery researchers have identified in this study includes proteins that can open or close this packaging.
Earlier work had shown that these protein complexes are important for Toxoplasma ’s survival, but it was not clear what function they had, or whether they performed the same or different roles in gene regulation. In this work, Schwarz and Lourido tackled this question by tracking how each complex interacts with the parasite’s genome and how gene activity changes when either one is disrupted.
When the researchers disrupted one complex, gene activity quickly dropped across much of the parasite’s genome, as would be expected for a regulator required to turn those genes on. When they disrupted the other complex, the effects were smaller but grew over time strongly affecting genes active during only part of the parasite’s cell cycle.
Even genes that are usually inactive during routine culture, like those that are activated during the parasite’s sexual stage, were impacted, suggesting that this complex helps keep certain genes in a bookmarked state for fast developmental transitions — almost like holding the page for future reading.
“This tells us that the two complexes have district functions but collaborate in very precise ways throughout the cell cycle to divide up the labor of gene regulation,” says Schwarz, who is also the lead author of the study.
It is still not clear how these molecular machines work with other gene regulators. But the findings are an important step toward understanding how gene activity could be disrupted at key moments in the parasite’s life cycle. That knowledge could one day help guide new strategies to prevent or treat T. gondii and similar parasitic infections.
About Whitehead Institute :
Whitehead Institute is a nonprofit, independent biomedical research institute founded in 1982. The institute advances pioneering research in cancer, developmental biology, genetics, genomics, and related fields, with a mission to pursue bold, curiosity-driven science that deepens our understanding of life and improves human health. Led by 24 principal investigators and a global community of trainees and scholars, Whitehead Institute maintains a teaching affiliation with Massachusetts Institute of Technology (MIT) but is fully independent in its research programs, governance, and finances.
Nature Communications
Two distinct SWI/SNF complexes direct chromatin-linked transcriptional programs in Toxoplasma