EBI-EMBL is an advanced undergraduate and postgraduate level class taught at the Universidad de los Andes in association with EBI-EMBL, the sessions are taught by both institutions face-to-face and virtual. The course aims to provide the student with the necessary tools to access the main databases of the European Bioinformatics Institute (EMBL-EBI), to promote in students the use of this information to generate discoveries. In addition, the student must create and develop a research project using the tools learned.
- Structural alterations and their effects on metabolic pathways caused by mutations in the major genes responsible for Leigh syndrome
Authors: Laura Valentina Acosta Corredor,Nicolas Aparicio Claros & Juanita Puentes Mozo
Leigh syndrome is a progressive neurometabolic disorder primarily affecting pregnant women and infants aged 3 to 12 months, characterized by muscle tone deficits, spasticity, and growth delays. Current treatment focuses on symptom management due to the polygenic nature of the disorder, with around 50 identified genes linked to oxidative phosphorylation pathways. However, the complex genetic diversity complicates the understanding of how mutations lead to the syndrome, making it difficult to identify specific therapeutic targets. This study reviews five major genes associated with Leigh syndrome using data from the European Bioinformatics Institute (EBI), analyzing structural information, biological roles, and known variants. By examining the impact of characteristic mutations on protein domains and their roles in the oxidative phosphorylation pathway, particularly in the formation and activation of complex III in the electron transport chain, this research enhances understanding of the molecular mechanisms of Leigh syndrome and supports the development of more effective therapeutic strategies.
Repo: https://github.com/naparicioc/Leigh_Syndrome_EBI video
- Use of bioinformatics tools for the study of alpha-1-antitrypsin deficiency
Authors: Verónica María Cabrera Amaya, María Alejandra Guevara Mayuza & Daniel Urdaneta Giraldo
Alpha-1-antitrypsin (AAT) is a vital blood protein encoded by the SERPINA-1 gene on chromosome 14q32.13, primarily produced in the liver, where it functions as a protease inhibitor with anti-inflammatory properties. The native form, known as "M," protects tissues by inhibiting elastase; however, mutations in the SERPINA-1 gene can lead to Alpha-1-antitrypsin deficiency (AATD), notably the "Z" or PIZ variant, which misfolds and accumulates in the liver, resulting in tissue damage. Individuals with two copies of the mutated gene (ZZ or "PIZZ") are at heightened risk for liver disease and lung conditions like emphysema, while those with one mutated copy (PIMZ) have a slightly elevated risk. AAT consists of 394 amino acids arranged into 7 alpha helices and 12 beta sheets, with the active site at methionine 358, which covalently bonds to elastase's serine 195. Misfolding, particularly in the Z variant, disrupts critical interactions that reduce enzyme activity. Recent research emphasizes AAT's role in inflammation, especially its release from neutrophils to inhibit elastase in lung and liver tissues, underlining its protective function. Understanding the genetic and structural factors influencing AAT's function is crucial for unraveling AATD complexities and may lead to targeted therapeutic interventions. Additionally, enhancing awareness and implementing preventive strategies for AATD could reduce health system burdens and improve patient outcomes.
- Bioinformatics study of mutations in the HEXA protein that cause Tay-Sachs disease
Authors: Juan Camilo Camacho, Silvia Cristina Rodriguez and Maria Camila Rincon
Tay-Sachs disease is a rare genetic disorder affecting babies and young children, leading to neurodegeneration, developmental delays, paralysis, and blindness due to the accumulation of GM2 ganglioside from a deficiency in hexosaminidase A, encoded by the HEXA gene. Mutations in this gene, especially prevalent among Ashkenazi Jews, result in dysfunctional enzyme activity. This study analyzes three specific HEXA mutations using EMBL-EBI tools to assess their impact on protein function. The HEXA gene has significant expression in the brain and immune cells, and the research includes structural analyses of beta-hexosaminidase A to understand its role in metabolism and interactions with GM2A activator, providing insights into Tay-Sachs disease for future research.