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Cultivation of human cells with deficiencies in DNA repair under conditions other than atmospheric oxygen

Grant number: 22/02311-2
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): May 01, 2022
Effective date (End): May 31, 2025
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Acordo de Cooperação: Netherlands Organisation for Scientific Research (NWO)
Principal Investigator:Carlos Frederico Martins Menck
Grantee:Gabrielly Cristine Martins
Host Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Federal de São Paulo (UNIFESP). São Paulo , SP, Brazil
Associated research grant:19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg), AP.TEM

Abstract

Cokayne Syndrome (CS) is an autosomal recessive disease, which is characterized by neurodegeneration, CS patients are characterized by having sunken eyes, microcephaly, prominent jaws, erythematous dermatitis on sun-exposed skin, failure in the growth process and delay cognitive, in addition to neuronal loss, calcification, spasms and tremors. The cause of CS disease is related to mutations in the CSB and CSA gene, in most cases it is due to mutation in CBS. With the mutation in these genes, there are implications for transcription-coupled repair (TC-NER) generating several problems for the individual. Cells deficient in CSB show an increase in reactive oxygen species, and accumulation of damaged mitochondria, making it possible to relate mitochondrial autophagy with CSB deficiency. In this project, the use of pluripotent stem cells (iPSCs), neuronal progenitor cells (NPCs) and organoids will be used as a methodology. However, the objective of the work is to analyze and observe if there are changes when cells and organoids are grown in a standard culture environment and under hypoxic conditions, since our brain works in hypoxic conditions. (AU)

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