PHD PROJECTS
DC1 | A spatial map of pathologic cell-cell interactions in lung tissue in asthma and COPD
Stockholm University, SE
Building on previous work mapping cell types of healthy lungs done at Stockholm University, this PhD project aims to create similar detailed maps for diseased lungs. The goal is to identify specific changes and areas affected by various lung diseases. The PhD student will then analyze existing data to predict how cells in these diseased areas communicate with each other. This involves validating and comparing the activity of certain genes in both healthy and diseased lung tissues. Finally, the project will investigate disease-related pathways to find potential targets for genetic or chemical treatments, which could lead to new therapeutic strategies.
DC2 | A multimodal analysis and functional dissection of cell circuits in COPD progression
Helmholtz Center Munich, DE
The goal of this PhD project is to understand how certain diseases affect stem cells in the small airways of the human lung. The student will use our existing data on COPD (a lung disease) to study how these stem cells work in both healthy and diseased lungs. They will conduct experiments using human lung tissue and lab-grown lung models. Techniques will include advanced methods to study individual cells and their proteins, as well as detailed imaging and data analysis. The aim is to find ways to fix stem cell problems in COPD, which could lead to new treatments and diagnostic tools.
DC3 | A multimodal tissue atlas of cellular neighbourhoods in airway wall in severe asthma
Karolinska Institute, SE
The goal of this PhD project is to create a comprehensive and detailed map of cell interactions and lipid molecules in the airway walls of asthma patients. This will be achieved using lung biopsies from the UBIOPRED study, which includes a wide range of clinical, transcriptional, metabolic, and proteomic data. By correlating this data with spatial information, we aim to gain a deeper understanding of asthma. We will use advanced techniques to analyze RNA expression (such as 10X genomics), immune-related proteins (using Miltenyi MACSiima), and lipid molecules (through DESI mass spectrometry imaging) in bronchial biopsies from patients with severe asthma. This approach will help us identify specific interactions between cells and lipid mediators that define different asthma endotypes. Ultimately, this project aims to uncover the complex cellular and molecular landscape of asthma, providing insights that could lead to better diagnosis and treatment options for patients.
DC4 | Transcriptomic & epigenetic biomarkers of hyper-inflammatory asthma endotypes driven by repeated viral infection
University Hospital Schleswig-Holstein, DE
The goal of this PhD project is to study how certain changes in our genes, specifically the overproduction of a protein called IL6 in the cells lining our airways, can worsen asthma over time. Using data from a large asthma study that has followed over 360 people for more than five years, the PhD student will check if these findings are consistent in other groups of children and adults from different studies, including those from Groningen and other international research projects. The student will also use common viruses that affect children, like RSV, to see how they cause the cells in our airways to produce too much IL6 and what the long-term effects are. This will be done using special lab techniques that mimic the conditions in our airways. Additionally, the project aims to develop a test to diagnose these genetic changes and use computer models to better understand the data, which could help in creating targeted treatments for asthma.
DC5 | Pre-COPD, early COPD and COPD biomarkers across the life-span
Barcelona Clinic Research Foundation, ES
This PhD project aims to understand how and why some people develop Chronic Obstructive Pulmonary Disease (COPD) from an early stage called Pre-COPD. We will study a group of 300 young smokers over several years, measuring their lung function every few years. We will also analyze samples from their noses, blood, and other fluids to find biological markers linked to Pre-COPD and COPD. By combining all this information, we hope to uncover the underlying causes of these conditions. Additionally, we will use lab models to see how certain pathways cause damage to lung cells. Our goal is to identify new targets for treatments that could stop the disease from getting worse.
DC6 | Transcriptional and epigenetic changes in airway wall in asthma across the lifespan
University Medical Center Groningen, NL
Asthma is a common, long-term disease that causes inflammation in the airways and often starts in early childhood. It varies widely due to different genetic and environmental factors, depending on when it begins. These variations, called endotypes, show specific patterns in the airway cells and immune responses. Recent research found that changes in nasal DNA can help diagnose allergic asthma, but this method's accuracy depends on age. More detailed studies are needed to understand how these DNA changes relate to asthma at different ages. The goal of this PhD project is to create early-life diagnostic tools and better understand asthma throughout life using advanced genetic analysis.
DC7 | An inflammation atlas of circulating immune cells for asthma and COPD biomarkers
Omniscope Spain, ES
This PhD project aims to create a detailed map of immune cells in the blood of asthma and COPD patients using advanced single-cell analysis techniques. This project will combine single-cell RNA sequencing with Adaptive Immune Receptor Repertoire (AIRR) sequencing to identify specific inflammatory cell types and immune signatures associated with these diseases. Over the next three years, the research will start with generating and analyzing standardized data, and then move on to developing a framework for discovering biomarkers and categorizing patients. Initially, the focus will be on thoroughly characterizing the inflammatory environments in asthma and COPD. Later, machine learning will be used to classify patients based on the integrated single-cell and AIRR data. The results of this project will enhance precision medicine by providing new tools for diagnosing and monitoring treatment responses in patients, and will improve our understanding of the inflammatory processes in chronic respiratory diseases.
DC8 | Resetting the immune system in severe exacerbating asthma: a unique asthma endotype
Bispebjerg Hospital Copenhagen, DK
Severe asthma is marked by ongoing airway inflammation, even with high-dose steroid treatment, and strong inflammatory responses to environmental triggers like viruses, leading to frequent severe asthma attacks. New treatments using monoclonal antibodies can stabilize patients by targeting specific immune pathways, offering a chance to understand why the immune system overreacts in severe asthma. This PhD project will explore the immune changes in patients with severe asthma, focusing on epithelial dysfunction and harmful immune responses. It will identify pathways linked to remission and suggest biomarkers for targeting new treatments in individual patients. By combining clinical data from patients treated with anti-IL4Ra (dupilumab) or anti-TSLP (tezepelumab) with advanced lab techniques like histological assays, transcriptomic analysis, and cell culture assays, this project provides training in cutting-edge methods.
DC9 | An integrated disease atlas of human lung tissue in asthma and COPD
University Medical Center Groningen, NL
This PhD project aims to create a comprehensive reference atlas for asthma and COPD. Building on our experience with the Human Lung Cell Atlas, we will compile a complete dataset of all available single-cell RNA sequencing (scRNA-seq) studies on asthma and COPD from RESPIRE-EXCEL partners and existing literature. This dataset, called the Human Airway Disease Cell Atlas (HADCA), will help us analyze the common and unique cell states, pathways, and interactions in these chronic airway diseases. We will explore these disease pathways for potential treatments through drug repurposing. To validate our findings, we will conduct follow-up studies using tissues or primary cells from patients. This project will provide a detailed understanding of the cellular mechanisms in asthma and COPD, guiding the development of new treatments.
DC10 | Comparative analysis of model systems to study COPD
Helmholtz Center Munich, DE
To develop treatments for diseases like COPD, we need to understand the molecular details of how these diseases work. This is usually done using model systems because of ethical and legal reasons. However, applying findings from these models to humans is challenging. In this PhD project, we will create a computational tool to compare different COPD models. This will help us choose the best model to study specific aspects of the disease. We will use single-cell genomics data from human COPD patients, mouse models, lab cultures, and precision-cut lung slices. By integrating this data, we aim to identify the most suitable models for studying COPD.
DC11 | Advanced bronchial epithelial cell culture models of asthma endotypes validated by transcriptional signatures
University Medical Center Groningen, NL
This PhD project aims to study how airway cells function in asthma patients. The student will grow bronchial cells from asthma patients and analyze their RNA to compare with those seen in actual patients. They will expose these cells to allergens and viruses and use CRISPR/Cas9 to understand the disease mechanisms. The goal is to validate these cell models for testing new treatments and developing biomarkers for personalized medicine. The project is part of a larger team with expertise in cell culture and data analysis to support the student.
DC12 | Cell circuits in the airway wall in early-stage COPD
National Center for Scientific Research, FR
The goal of this PhD project is to study the early changes in the airways of people who are just starting to develop Chronic Obstructive Pulmonary Disease (COPD). By understanding these early changes, we hope to find new markers and treatment targets for this chronic lung condition. The project will use detailed maps of cells from COPD patients' airways to identify problem areas and pathways. Lab models will help us see how these cells react to cigarette smoke. The PhD student will combine this information with long-term patient data to link cellular changes to real-life outcomes. This project offers a unique chance to learn both lab techniques and computer analysis, skills that are highly valued in today's biomedical field.
DC13 | Gene regulatory networks driving pathological cell behaviour in asthma and COPD
The Chancellor Masters and Scholars of the University of Cambridge, UK
Single-cell RNA sequencing (scRNAseq) helps us understand gene expression in specific cell types and diseases. At the same time, genome-wide association studies (GWAS) have found genetic variants linked to disease development. However, combining these different types of data to identify the best drug targets is challenging. We plan to use gene regulatory network (GRN) models for the lungs and airways, both in healthy and diseased states (asthma and COPD), to integrate these data sets. Additionally, we will use machine learning and generative AI to predict how these networks respond to different interventions. These predictions can then be tested in laboratory models to find the best points for treatment and predict their effects. This approach aims to streamline the identification of promising drug targets and improve treatment strategies.
DC14 | Treatment response to anti-IL5 (Mepolizumab) in patients with severe asthma
Imperial College London, UK
The PhD project aims to understand how a specific treatment, called T2 biologics, works in patients with severe asthma. This information will help create a detailed map of airway diseases and introduce new treatment options. Researchers have collected samples from patients before and after they started a therapy called mepolizumab. They will compare these samples to see how well the treatment works. By analyzing blood and tissue data, they hope to find markers that predict who will respond to the treatment. Other ongoing studies will also contribute data to this project. The combined information will help identify which cells and pathways are affected by the treatment, leading to better-targeted therapies for severe asthma.
DC15 | Towards precision medicine for COPD: treatment responses to anti-TSLP
University of Leicester, UK
This PhD project aims to understand how certain proteins, called alarmins, contribute to inflammation in COPD patients. These proteins can worsen health by triggering different types of inflammation. The goal is to find ways to target these alarmins with precision medicine. Researchers will study how alarmins affect various immune cells and tissues, both in lab settings and in real-life conditions. They will measure alarmins in blood and sputum samples during stable periods and flare-ups of the disease. By analyzing this data, they hope to identify different patient types and see how these proteins affect the body's response to viruses. Finally, they will look at how these mechanisms relate to treatment responses, aiming to improve therapies for COPD.