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A network for an integrative biology in neglected diseases: bridging epigenetics, metabolism and cell cycle in pathogenic trypanosomatids

Grant number: 18/14432-3
Support type:Research Projects - Thematic Grants
Duration: April 01, 2019 - March 31, 2022
Field of knowledge:Biological Sciences - Parasitology
Cooperation agreement: MRC, UKRI ; Newton Fund, with FAPESP as a partner institution in Brazil
Principal Investigator:Ariel Mariano Silber
Grantee:Ariel Mariano Silber
Principal investigator abroad: Michael Barrett
Institution abroad: University of Glasgow, Scotland
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Julia Pinheiro Chagas da Cunha ; Luiz Ricardo Orsini Tosi ; Maria Carolina Quartim Barbosa Elias Sabbaga ; Otavio Henrique Thiemann


Pathogenic trypanosomatids such as Leishmania spp. and Trypanosoma cruzi are the causative agents of leishmaniosis and Chagas disease, a group of neglected diseases endemic in the tropical and subtropical belt of the planet and the Americas, respectively. The therapeutic approaches against these diseases are largely unsatisfactory due to toxicity and emergence of resistance. Thus, new drugs are urgently needed against these threats. In the last 20 years, a profusion of OMICS approaches resulted in a deeper comprehension of cellular processes allowing the survival of these parasites in their hosts, a sine qua non condition for establishing the infection and triggering the pathology. However, most of these studies approached cellular processes individually; as a consequence our comprehension of their integration is poor. The goal of this proposal is to understand the interaction among three essential core processes: metabolism, cell cycle and epigenetic gene expression regulation, with the goal of establishing a broader comprehension of how the metabolic environment affects parasite proliferation and determines inheritable adaptations. The information to be obtained will be fundamental to elucidate the basic biology of these pathogens as well as to discover new druggable points, greatly contributing for the development of novel therapies. (AU)

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