Researchers find gene that prompts the African sleeping sickness parasite to convert to its dormant phase

Researchers find gene that prompts the African sleeping sickness parasite to convert to its dormant phase
Dynamic subnuclear localization of grumpy during parasite differentiation. (A) Transcript-level changes during the transition from slender to stumpy forms, measured by RT-qPCR. Stumpy formation was induced by pCPT-cAMP (C3912, Sigma-Aldrich). Tb927.2.2220 is used as a control to normalize transcript levels (73). PAD1 and GFP genes are used as controls to estimate parasite differentiation into stumpy forms. Tb927.10.12080 is the gene upstream of grumpy. Results are shown as means (SEM, n = 3 except for the 48-hour time point, n = 2). Dunnett’s multiple comparisons test was used for statistical analysis using the 0-hour time point as the control for comparison (adjusted P values: *P < 0.05; **P < 0.01; ****P < 0.0001). (B) Subcellular localization of grumpy during the transition from slender to stumpy forms using RNA-FISH. Time points (0, 12, 24, 36, and 48 hours) of parasite differentiation after addition of the pCPT-cAMP stimulus to the culture medium. DIC, differential interference contrast microscopy image of T. brucei; GFP, GFP::PAD1 signal expressed in the nucleus of stumpy forms; GRUMPY, grumpy signal using RNA-FISH (Stellaris probes). (C) Quantification of the intensity of the nucleolar grumpy RNA-FISH signal corrected with the cytoplasmic signal, during stumpy formation induced by pCPT-cAMP at time 0, 24, and 48 hours. Statistical test: one-way analysis of variance (ANOVA) (Dunnett’s multiple comparisons test), adjusted P value: ****P < 0.0001. Credit: Science Advances (2022). DOI: 10.1126/sciadv.abn2706

A team of researchers from Portugal, Israel, Poland and Spain has found the gene that prompts the parasite Trypanosoma brucei to change from its normal long, slender shape to one that is short and stumpy. In their paper published in the journal Science Advances, the group describes how they found the gene and their hope that doing so will lead to a cure for African sleeping sickness.

African sleeping sickness is caused by Trypanosoma brucei transmitted by tsetse fly bites. People afflicted initially show no symptoms, giving the parasite time to multiply. Eventually, it makes its way to the brain, leading to personality and and sleep disorders. If left untreated, it is fatal. Prior research has shown that once the parasite reaches a certain saturation point in the body, individual kinetoplastids begin to change shape from a long, slender appearance to a shorter and stumpier form. Researchers have been studying the transformation in hopes of determining a way to get the parasite to transform earlier, because in its stumpy form, it cannot reproduce. In this new effort, the researchers found the gene responsible for initiating the shift.

The researchers found the gene by taking a closer look at so-called junk DNA—parts of the genome labeled as non-coding, and thus not likely to be of use to researchers. They analyzed the RNA produced via instructions from the genome at such sites and found 1,428 possibilities, which they narrowed to 399. They were then able to find one they called "grumpy" by studying nearby that were already known to play a role in the process of transformation. They confirmed their find by artificially increasing the same type of RNA in a parasite sample in mice and found that it induced the change to the stumpy form.

The findings are still preliminary—next, the researchers plan to determine whether upping the RNA samples in humans works equally well. They are also looking at developing tests to diagnose infections earlier, before occurs.

More information: Fabien Guegan et al, A long noncoding RNA promotes parasite differentiation in African trypanosomes, Science Advances (2022). DOI: 10.1126/sciadv.abn2706

Journal information: Science Advances

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Citation: Researchers find gene that prompts the African sleeping sickness parasite to convert to its dormant phase (2022, June 17) retrieved 31 March 2023 from
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