Our understanding of the importance of non-coding RNAs (ncRNAs) in multiple biological processes has grown exponentially in recent years. Because of their preponderance, it is not surprising that almost all biological functions are in one way or another under the control of these molecules. Although they vary greatly in origin, biogenesis and mode of action, they can be roughly separated into two families based on size. At one end of the spectrum are the small ncRNAs, which are 20-30 nucleotides (nt) in size, and at the other end are the long ncRNAs, which group all RNAs larger than 200 nt. Since research on lncRNAs began, their importance in the context of viral infection has been the subject of particular attention. Indeed, by their nature, viruses are strictly dependent on a host cell to translate their genome, replicate, and generate new viral particles for propagation. In our research team, we study how a viral infection can impact biological pathways involving small ncRNAs. Our study models are viruses associated with several pathologies that represent a threat to human health. We are interested in two types of viruses:
i) DNA viruses, such as Kaposi’s sarcoma virus (KSHV) and cytomegalovirus (CMV)
ii) RNA viruses transmitted by arthropods such as Sindbis virus (SINV), Chikungunya virus (CHIKV), Zika virus (ZIKV) or tick-borne encephalitis (TBEV).
The results of our work help us to better understand the molecular mechanisms involved in the viral replicative cycle and also how the infected organism responds to viral infection at the cellular level. In the long term, we hope that our research will help develop new therapeutic approaches against viruses.
The objectives of the research team are multiple and consist on the one hand in understanding the regulation of a family of small RNAs, called microRNAs, during viral infection, and on the other hand in elucidating the importance of an antiviral defense mechanism based on the production of small interfering RNAs (siRNA) in mammals. Four major research axes can be distinguished in the team:
Axis 1 To understand how viral microRNA biogenesis can be regulated at the post-transcriptional level.
Axis 2 Identify and unravel the mechanisms involved in the degradation of cellular and viral RNAs, and their involvement in infection.
Axis 3 Address the question of the antiviral role of RNA interference in mammals and identify regulators of this activity.
Axis 4 Study of double-stranded RNA recognition and regulation in mammalian host-virus interactions
Uelewa wetu wa umuhimu wa RNA zisizo za kuhariri (ncRNAs) katika michakato mingi ya kibiolojia umekua kwa kasi katika miaka ya hivi karibuni. Kwa sababu ya ukubwa wao, haishangazi kwamba karibu kazi zote za kibiolojia ziko kwa njia moja au nyingine chini ya udhibiti wa molekuli hizi. Ingawa wao hutofautiana sana katika asili, biogenesis na njia ya hatua, wanaweza kuwa roughly kutenganishwa katika familia mbili kulingana na ukubwa. Katika mwisho mmoja wa wigo ni ndogo ncRNAs, ambayo ni 20-30 nucleotides (nt) kwa ukubwa, na katika mwisho mwingine ni ndefu ncRNAs, ambayo kundi wote RNAs kubwa kuliko 200 nt. Tangu utafiti juu ya lncRNAs kuanza, umuhimu wao katika muktadha wa maambukizo ya virusi imekuwa mada ya tahadhari maalum. Kwa kweli, kwa asili yao, virusi hutegemea sana chembe ya mwenyeji kutafsiri genome yao, kuiga, na kuzalisha chembe mpya za virusi kwa ajili ya kuenea. Katika timu yetu ya utafiti, tunajifunza jinsi maambukizo ya virusi yanaweza kuathiri njia za kibiolojia zinazohusisha ncRNA ndogo. Mifano yetu ya utafiti ni virusi vinavyohusiana na magonjwa kadhaa ambayo yanawakilisha tishio kwa afya ya binadamu. Virusi vya DNA (Kosmos sarcoma virus, Kshv) na virusi vya RNA (Cytomegalovirus, CtMV) ni virusi vinavyosambazwa na wanyama aina ya Sindhi (SINV), Chikungunya (CHIKV), Zika (Zika) na TBE (Tick-borne encephalitis). Matokeo ya kazi yetu yanatusaidia kuelewa vizuri utaratibu wa molekuli unaohusika katika mzunguko wa replication ya virusi na pia jinsi kiumbe aliyeambukizwa anajibu maambukizi ya virusi katika ngazi ya seli. Kwa muda mrefu, tunatumaini kwamba utafiti wetu utasaidia kuendeleza mbinu mpya za matibabu dhidi ya virusi. Lengo la utafiti ni nyingi na ni pamoja na kuelewa udhibiti wa familia ya RNA ndogo, inayoitwa microRNA, wakati wa maambukizo ya virusi, na kwa upande mwingine kuelezea umuhimu wa utaratibu wa ulinzi wa antiviral kulingana na uzalishaji wa RNA ndogo ya kuingiliana (siRNA) katika mamalia. Mifumo minne ya utafiti inaweza kutofautishwa katika timu: Mfumo wa 1 Kuelewa jinsi viini vya virusi vinavyoweza kudhibitiwa katika kiwango cha baada ya maandishi. Mfumo wa 2 - Kutambua na kufunua taratibu zinazohusika katika uharibifu wa RNA za seli na virusi, na kuhusika kwao katika maambukizi. Mfano wa tatu ni kugundua athari za RNA kwa wanyama wa mnyama na kuamua ni nini kinachohusika na athari za RNA. Mfano wa 4 - Utafiti wa utambuzi wa RNA ya mnyororo wa mbili na udhibiti katika mwingiliano wa virusi vya mama na majeshi