SCIENTIFIC BASIS:
Chronic airway diseases such as severe asthma and Chronic Obstructive Pulmonary Disease (COPD) are characterized by neutrophil-dominated lung inflammation. Neutrophils are the most abundant circulating white blood cells and possess powerful antimicrobial weapons such as phagocytosis, degranulation, production of Reactive Oxygen Species (ROS) and formation of Neutrophil Extracellular Traps (NETs). However, when dysregulated, these same defense mechanisms can cause tissue damage and contribute to disease.
Exposure to Particulate Matter (PM) air pollution exacerbates these inflammatory responses and poses a huge burden on public health. Patients with existing chronic lung conditions are particularly vulnerable. This project investigates how real-world PM from diverse global sources triggers harmful neutrophil activity, and aims to identify strategies to mitigate detrimental PM-induced inflammation without compromising essential immune defense mechanisms to improve lung health.
TECHNIQUES AND SKILLS:
The student will gain expertise in immune cell isolation and culture, flow cytometry, protein and gene expression analyses and advanced microscopy. Neutrophils will be isolated from blood samples, airway epithelial cultures will be grown at air-liquid interface (ALI), and co-culture systems involving different immune cells will be utilized. They will also develop critical skills in experimental design, data analysis, and scientific communication.
AIMS:
1) Investigate how real-world Particulate Matter (PM) from different sources globally, e.g. urban or forest burning locations, impact the functions of neutrophils.
2) Identify molecular signaling pathways that directly or indirectly influence neutrophil function.
3) Compare PM-induced activation of neutrophils from healthy donors and patients with chronic airway disease and identify strategies to ameliorate excess inflammatory responses.
OBJECTIVES:
Year 1: Establish essential methodologies including the isolation of donor neutrophils, inducing ALI cultures, and characterizing the heterogeneity of real-world PM samples.
Year 2: Understand the impact of PM on neutrophil functions directly and in co-culture systems with relevant airway cells.
Year 3: Determine the molecular pathways through which PM affects neutrophil function.
Year 4: Comparing responses to PM between neutrophils from healthy individuals versus asthma and COPD patients we aim to identify public health interventions that can mitigate against detrimental effects.
3-MONTH ROTATION PROJECT:
The student will establish neutrophil isolation and optimize quantitative microscope methods to measure NET formation in response to PM from various sources. This project will provide foundational techniques and pilot data for the main PhD study.
