Banca de DEFESA: Matheus de Castro Leitão

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : Matheus de Castro Leitão
DATE: 29/01/2024
TIME: 14:30
LOCAL: Auditório número 2 - IB
TITLE:

"Identification of safe genomic regions for synthetic biology applications"

KEY WORDS:

Genomic Safe Harbour, Python, S. cerevisiae, Synthetic Biology

PAGES: 83
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Since the beginning of genetic engineering, the insertion of exogenous genes into host cells has presented challenges, whether due to the increase in the size of the insertions or the challenge of precise targeting for integration into regions of the genome that are permissive for transcription. With the advent of Synthetic Biology, there has been an increase in the complexity of inserting not just one gene, but several genes that are components of metabolic pathways 83 and genetic circuits, as well as the need for more refined studies of genomic organization, structuring, and regulation. Specific integration without modifying the expression of endogenous genes coding for essential proteins is required to avoid random integration into the genome that could generate unstable expression or unpredictable phenotypes. A common approach is to target insertions to intragenic or intergenic regions capable of accommodating the expected expression of the insert without adverse changes to the host, known as the Genomic Safe Harbor (GSH). GSHs have been found in humans, mice, monkeys, and Cryptococcus, but most of them are in regions with high gene density and, in the case of humans, close to cancer-related genes. To expand the number of GSHs available in different organisms, this proposal aimed to develop a program to identify probable GSHs with an optimized approach following defined criteria to refine the search for new extragenic insertion regions in three eukaryotic organisms: human, mouse, and Saccharomyces cerevisiae. This program, SHIP (Safe Harbor Identification Program), was developed in the Python language and used gene annotation files from the studied organism as input, together with information on gene expression regulatory characteristics, such as DNA methylation potential, transcription factor binding sites, and histone alteration sites, identifying six pGSHs in Saccharomyces cerevisiae, 16 in Homo sapiens and 11 in Mus musculus. In addition, this proposal validated in vivo 5 GSHs identified by the SHIP program in the model organism S. cerevisiae. Thus, the SHIP program is the first available, experimentally validated, user-friendly algorithm capable of identifying pGSHs in any eukaryotic organism with genomic annotation.

COMMITTEE MEMBERS:
Presidente - 1556610 - GEORGIOS JOANNIS PAPPAS JUNIOR
Interna - 1207115 - ILDINETE SILVA PEREIRA
Externo à Instituição - JOÃO RICARDO MOREIRA DE ALMEIDA - EMBRAPA
Interno - 2122537 - MARCELO DE MACEDO BRIGIDO