Gene Expression and Protein Profiling of Phosphatidyl-Inositol-phosphate-kinases (PIPKins) in Adults and Neonates

• Grant number: 23/05315-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2023
• End date: August 31, 2024
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Susan Elisabeth Domingues Costa Jorge
• Grantee: Leonardo de Oliveira Alves
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities, AP.TEM

Abstract

Human hemoglobin (Hb) is the protein responsible for transporting oxygen in the blood. Its structure is based on tetramers of peptide chains whose genes are expressed according to the stage of development. Adult hemoglobin (HbA) is formed by two alpha (±) chains associated with two beta (²) chains and represents more than 95% of the total Hbs of the adult. Fetal hemoglobin (HbF) is formed by two alpha chains associated with two gamma (³) chains and is found in adults in less than 1% of the total globins in the blood. This variation is particularly relevant in the fetal period due to its greater capacity to bind O2, allowing the transport of this gas across the placenta. As a consequence of the observation of this property of HbF and its structural difference in relation to HbA, the increase of expression of the HBG genes (of the ³ chains, of HbF) has been seen as a great potential target therapeutic for haemoglobinopathies involving the HBB genes (of the ² chains of HbA), such as Sickle Cell Anemia and ² Thalassemia. In light of this, the Laboratory of Hemoglobinopathies - Department of Pathology, Faculdade de Ciências Médicas (Unicamp) has been dedicated to the study of Phosphatidylinositol-Phosphate Kinases (PIPKins) as potential modulators of human Hb genes. Therefore, the present study aims to evaluate the expression profile of PIPKins and globin genes in reticulocytes from 30 samples from newborns compared to 30 samples from adults, with normal blood count. In this way, it will be possible to assess whether there is any evidence of natural differential expression of PIPKins in the globin switching process. Such results should compose part of the M.S.c project that foresees the silencing of PIPKins in CD34+ erythroid precursors.