Cell cycle dependent transcriptional regulator regulates encystation

( 12.22.25  )                                    Written by Gio Kim          

Giardia Lamblia is a parasite that causes diarrhea and commonly spreads through contaminated water, food, or direct contact. It survives in different environments through two forms: the active trophozoite, which is when Giardia lives in the host’s small intestine, and the dormant cyst, which survives outside the host. To survive environmental changes, Giardia goes through encystation (the process of forming a cyst).  The cyst wall is composed of about 37% cyst wall proteins (CWPs) and 63% sugar polymers made from N-acetylgalactosamine (GalNAc).

Encystation is closely linked with the cell cycle, and as encystation starts, more cells accumulate in the G2+M phase, which allows them to produce cyst wall proteins efficiently. During this process, Transcription factors (TFs) play a key role by turning genes on or off during this stage.

​In this study, the researchers screened 6 early response TFs: MYB1, GLP3, GLP4, PAX1, ARID2, and E2F1. By measuring where each TF was located in the parasite using fluorescent markings, the researchers discovered that GLP4 and MYB1 entered the nucleus quickly after encryption began. They measured TF levels at different time points and found that GLP4 increased within 30 minutes after encryption, which was earlier than MYB2, a TF previously known to activate cyst wall genes.

​Using CRISPRi and CasRX techniques to reduce the levels of TFs, the researchers found that when GLP4 decreased, MYB2 and cyst wall proteins increased, and more cells formed mature cysts. An overdose of GLP-4 caused the direct opposite effect, decreasing MYB2 and cyst wall protein levels.

​With this discovery and the tracking of cell cycles using flow cytometry, the researchers demonstrated that GLP4 is a cell cycle dependent repressor that limits entry into encryption by controlling the level of MYB2. This new discovery could provide future solutions to inhibit Giardia Lamblia’s transition into a cyst and prevent the disease from spreading.

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You can read the full paper here:

https://pmc.ncbi.nlm.nih.gov/articles/PMC9295799/#abstract2