Investigation of the combinatorial effects of oxidative stress, aging, and app mutations on blood-brain barrier function

• Grant number: 23/12354-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: January 19, 2024
• End date: June 28, 2024
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Lucimara Gaziola de la Torre
• Grantee: Gabriela Gomes da Silva
• Supervisor: Peter Charles Searson
• Host Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Johns Hopkins University (JHU), United States
• Associated to the scholarship: 21/02795-7 - Brain-on-a-chip microfluidic platform for mimicking the blood-brain barrier, BP.DD

Abstract

The aging of the world's population and the development of degenerative diseases such as Alzheimer's, whose cure is still unknown, have required the creation of new strategies that make it possible to study them more efficiently and quickly. However, developing new drugs to prevent and treat these diseases depends on drug delivery strategies that can cross the blood-brain barrier (BBB). This semipermeable, highly selective barrier interfaces peripheral blood circulation and the central nervous system (CNS). Technological advances in the microfluidic area have enabled the construction of microenvironments that mimic human conditions in vivo and contribute as a tool for understanding the functioning of the BBB and studies on the permeation of new drugs. In this context, this research project has as its main objectives (i) construction of a hydrogel-based microfluidic device to mimic the BBB; (ii) obtaining the human induced pluripotent stem cell-derived brain microvascular endothelial-like cells (iBMECs); (iii) culturing the iBMECs on the microfluidic device to mimic the brain microvessels; (iv) modeling acute and chronic oxidative stress on brain microvessels; (v) modeling the combinatory effect of oxidative stress, aging, and APP mutation on brain microvessels. This project will be developed in collaboration with Professor Peter Searson's research group from Johns Hopkins University (JHU, USA). It is hoped that this project can contribute to understanding Alzheimer's disease by modeling some perturbations on BBB associated with this disease. (AU)