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Ososayensi bacwaninga ukuthi umalaleveva uwagqekeza kanjani ama-cells ukuse bezokwandisa izindlela zokuwelapha

Zulu translation of DOI: DOI: 10.1101/2020.08.31.275867

Published onJul 26, 2023
Ososayensi bacwaninga ukuthi umalaleveva uwagqekeza kanjani ama-cells ukuse bezokwandisa izindlela zokuwelapha
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Ukuhlola kwe-CRISPR-Cas9 kuthola i-CENPJ njengomulawula umzimba onokuhleleka kwmashubhana ngesikhathi se-Plasmodium ekuthelelekeni kwesibindi

Ngaphambi kokuqala ngomalaleveva onezinkomba, iqanda le-plasmodium elilodwa lingena  kwe-hepatocyte lichamsele libe ama-merozoites ayisigidi, ngangxenye ngokuhamba idla izinsiza zalo ezihleli kuye.

Sikhombisa ukuthi amashubhana omzimba azihlela ngenye indlela azungeze lesisimuncagazi (LS) esisesibindini.

Ngokusebenzisa indlela yokuhlola i-genome-wide CRISPR-Cas9, sithole abalawuli be-cytoskeleton, abe-vesicle trafficking, ER/Golgi stress ne-lipid biogenesis ezilawula ukwakheka kwe-Plasmodium LS.

Lezi zindlela ezintsha zokulawula ukutheleleka, okufakwa kuzo i-Centromere Protein J (CENPJ), isiholele ekuphenyeni ukuthi ama-microtubule organising centers (MTOCs) alawulwa kanjani ngesikhathi sokutheleleka.

Ama-Foci amashubhana e- γ-tubulin ahleli onqenqemeni lwesimuncagazi; ukuphela kwe-CENPJ kudlondlobalise lokhu okwenzekile nokutheleleka.

Uma kuqhutshekwa, sikhombisse ukuthi i-Golgi isebenza njenge-non-centrosomal MTOC ngokuhlela ama-γ-tubulin akhuthaze ne-nucleation yamashubhana onqenqemeni lwezimuncagazi.

Ngokuhlanganyela, sikhombisa ukuthi i- Plasmodium LS ibutha ama-Golgi ukuthi akhande ama-MT mediated conduits eqoqelana kwi-PVM, ukweseka lesi sigaba sokwakheka kwasesibindini.

Esikutholile kuphakamisa ukuthi ama-host targeted pharmacological inhibators angavimba ukutheleleka nge-LS.


Ososayensi bacwaninga ukuthi umalaleveva uwagqekeza kanjani ama-cells ukuse bezokwandisa izindlela zokuwelapha

Izimuncagazi eziningi zisebenzisa imisoco yabantu noma yesilwane ezihleli kuzo, ukuze zizalane.

Kulolu cwaningo abacwaningi bakhombe izakhi zofuzo ezithize ezidlala indima ukuthelekeleni ngomalaleveza ezakheni zesibindi, okungaholela emithini evikela ukuthola umalaleveva esikhathini esizayo.

Umalaleveva isifo esandile futhi esinobungozi empilweni esidalwa isimuncagazi i-Plasmodium, esitholakala ngokudliwa imiyane.

Uma ingena emzimbeni, i-Plasmodium iya esibindini iyozalela - lesi s’khathi siyikhethelo emithini evikela ukuthola umalaleveva ngoba izinkomba zesifo sizuke zingakaveli nesifo sisuke singeke sidluliseke.

Kulolu cwaningo, abacwaningi bebefuna izinguquko ezithize ezakheni zofuzo nakumaphrotheni  ezakheni zesibindi ezithelelekile, ezingashintsha indlela isifo esikhula ngayo.

Ukusebenzisa i-CRISPR-Cas9 ubuchwepheshe ubuguqula izakhi zofuzo, abacwaningi bakwaze ukucima izakhi zofuzo ezithize ukuze babone kushintshani uma lezo zakhi zingasebenzi.

Babe sebethelela izakhi zofuzo zesibindi eziphilayo nezingaphili ngezimuncagazi zamalaleveva.

Abebekunake kakhulu izinguquko ekwakhekeni kwama-microtubules (MT).

Lezi zinto ezisamashubu zibandakanyeka ezintweni eziningi okubalwa kuzo, ukuhambisa imisoco nokunye ezakheni zomzimba, futhi zijwayele ukwakhela kwi-nucleus yesakhi.

Okutholwe kuhamba phambili ukuthi i-Plasmodium izuma lamashubhana ezakhini - zesibindi esikhundleni sokuthi aqoqelane ngaphandle kwe-nucleus ezihambisa imisoco lapho edingwa izakhi khona, amashubhu aqoqelana ngaphandle kwezimuncagazi ziziphe imisoco yokuzalela.

Abacwaningi babone ukuthi uma bewisa iphrotheni ebizwa nge-CENPJ, isimuncagazi sikwaze ukuqoqela amashubhana amaningi kuso, izimucagazi zakhula kakhulu zaziphindaphinda kakhulu.

Abacwaningi bokhombe ezinye izakhi ezinomthelela ekutheni ukuthelelwa i-plasmodium kuba kubi kanjani.

Abacwaningi bake bakhombisa ngaphambilini ukuthi ezinye izimuncagazi zihlela amashubhana ukujikisa izinsiza ezisezakhini zize kuzona.

Kulolu cwaningo, abacwaningi baqinisekise ukuthi izimuncagazi ze-Plasmodium zingasebenzisa lendlela ukujikisa imisoco ukuze zizikhulise zona.

Esikhathini esizayo, ososayensi bathembele ekusebenziseni ukuqonda kwabo ngendlela izakhi zofuzo nezimuncagazi ezisebenzisana ngayo ngaphakathi ukuze kukhonjwe imithi emisha kamalaleveva.

Yize abacwaningi bekhombe ezinye izinguquko ezakheni zamaphrotheni esibindi ngesikhathi umalaleveva usanda kungena, kusadingeka umsebenzi omkhulu ukuqonda ukuthi i-Plasmodium iyiguqula kanjani i-cell chemistry nokusebenza ukuze kutholakale izinto izingaqondwa imithi.

Kusashona amakhulu ezinkulungwane zabantu ngonyaka ngenxa kamalaleveva, izibalo ezinkulu zalokhu zise-Afrika.


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