| Grant number: | 15/18641-8 |
| Support Opportunities: | Regular Research Grants |
| Start date: | August 01, 2016 |
| End date: | July 31, 2018 |
| Field of knowledge: | Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms |
| Principal Investigator: | Maria Isabel Nogueira Cano |
| Grantee: | Maria Isabel Nogueira Cano |
| Host Institution: | Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil |
| City of the host institution: | Botucatu |
| Associated researchers: | Claus Azzalin ; Elton José Rosas de Vasconcelos |
Abstract
Protozoan from Leishmania genus belong to the Trypanosomatidae family and present peculiar biological characteristics that are not shared with other eukaryotes. Many Leishmania species are the causative agents of a spectrum of diseases known as leishmaniases which are transmit by insects. The disease presents different clinical manifestations and in Brazil several new cases occur each year, principally due to social economic conditions, malnutrition, migration, environmental and climate changes. There are no efficient vaccines or treatment protocols and the drugs actually used to treat the disease are highly cost and usually lead to toxicity and parasite resistance. Therefore, to improve the knowledge about Leishmania molecular biology and physiology is crucial for the development of new therapies and to find parasite-specific drug targets. Actually, telomeres have been considered potential molecular targets as they are responsible to maintain genome stability. Leishmania telomeres similarly to other eukaryotes, are nucleoprotein structures found at the end of the chromosomes composed by protein complexes associated with repetitive DNA (5'-TTAGGG-3'). Telomeres protect chromosome ends from fusion and degradation ensuring that the genetic information is correctly copied during the cell cycle progress. Telomerase is the enzyme responsible to maintain telomere length, which can be controlled by different mechanisms such as the action of long non-coding telomeric RNAs (LncRNA). Among the telomeric LncRNAs are the Telomerase RNA component (TER) which is crucial for telomerase activity because it contains the template sequence that is copied by telomerase during telomere elongation. TERRA, the Telomere Repeat containing RNA and its counterparts, are also involved with telomere length regulation, telomere damage response and alterations in the composition of telomeric chromatin. In Leishmania we have previously identified and partially characterized LeishTER (Leishmania telomerase RNA), and here we propose to verify if the knockdown and overexpression of LeishTER alter its interactions with telomerase RNP and/or disturb parasite telomere homeostasis. In relation to TERRA expression in Leishmania, although it was shown more than two decades ago that trypanosomatids telomeres are transcribed by different types of RNA polymerase, at that time it was not clearly defined the transcription initiation site and which telomeric strand was transcribed. Here we will test the existence of TERRA in Leishmania using independent RNA-Seq libraries and will try to identify putative TERRA transcripts using northern blot, RT-PCR and RNA-FISH. The functions of both LncRNA telomeric RNAs will be studied using both parasite life stages and during promatigotes cell cyle. (AU)
| Articles published in Agência FAPESP Newsletter about the research grant: |
| More itemsLess items |
| TITULO |
| Articles published in other media outlets ( ): |
| More itemsLess items |
| VEICULO: TITULO (DATA) |
| VEICULO: TITULO (DATA) |