Groningen Research Institute for Asthma and COPD (GRIAC)
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Research programme
Mission and objectives
The mission of Groningen Research Institute of Asthma and COPD (GRIAC) is the multidisciplinary study of all aspects
of obstructive airway and pulmonary diseases through interaction between clinicians and fundamental researchers.
Research takes place at the interface of fundamental and applied patient-related research. A central goal of the research
is to translate fundamental findings into the clinical situation, and vice versa. The main theme is unravelling the underlying
mechanisms of the development and progression of airway obstruction, allergy, and airway yperresponsiveness,
and their mutual interactions. These phenomena constitute, in interaction with environmental factors, risk factors for
the development of asthma and COPD and are crucial characteristics in their clinical pictures.
Research area
The focus of research is on asthma and COPD, which involves the sub-programmes:
- 1. Epidemiology - Epidemiological studies on endogenous, environmental and lifestyle risk factors, both in general and patient-based populations, from prenatal onwards to old age.
- 2. Genomics - Studies on genes, gene expression and function, molecular mechanisms and gene-gene and gene-environment interactions in disease development, progression, remission, and severity, as well as disease intervention (pharmaco- genomics).
- 3. Pathophysiology and pathogenesis of allergen, smoking and other lifestyle factors, and environment-induced diseases - In vivo studies in humans and animal models using mice and unrestrained guinea pigs. Investigations include lung
function techniques and studies of blood, tissues and/or cells derived from airways or lungs. Furthermore, in vitro
studies assess cellular activation and interaction as well as signalling pathways in cells and tissue explants (e.g.
lymphocyte subsets, epithelial cells, fibroblasts, intact airway, and smooth muscle preparations). Interactions of
different cell types are studied in cells obtained by sputum induction as well as airway and lung tissue obtained by
bronchoscopy, by surgical biopsy or autopsy. - 4. Assessment, modulation and intervention in disease severity, progression and remission - Disease outcome assessment is being studied with techniques such as exhaled breath analyses and small airway function. In addition, validated questionnaires on Quality of Life, drug side effects, hyperresponsiveness and symptoms are developed for diagnostic purposes as well as outcome assessment. Interventions can be at the level of cell cultures, animal models and clinical studies with targeted therapy.
The main strategies to reach our goals are discussed below:
Genomics
The availability of genetic techniques and the collaboration with the Department of Genetics (Head: Prof. C. Wijmenga) have greatly extended the genetic sub-programmes, allowing genome-wide association studies, high throughput genetic SNP detection, fine-mapping in relevant chromosomal regions and candidate gene studies. Deep sequencing techniques and analysis strategies are currently being developed. The availability of and collaboration with the bio-informatics group of Prof. Ritsert Jansen is important for adequate data-mining, which is essential for genomics and proteomics research. Since gene-environment interactions are important for understanding complex diseases like asthma and COPD, these have been explored in several sub-programmes, in collaboration with multiple groups in the Netherlands and abroad. This has resulted in gene-environment interaction studies on atopy and asthma, and on COPD onset and progression. The GRIAC group collaborates internationally and takes the lead in some EC-funded FP6 (asthma: GABRIEL) and FP7 (COPD: COPACETIC) projects on genetics of asthma and COPD, and in exploration of specific gene-environment interactions in these projects.
Molecular biology techniques
Molecular biology techniques are being used more effectively and widely, and are being introduced when not present (either in our own labs or as part of local facilities; for example, the recently developed custom micro-array development and accompanying data-mining). In vivo and in vitro silencing of genes are now established techniques that are operational at the University Medical Centre and Pharmacy. This has enabled the use of RNAi and pharmacological modulation of membrane and nuclear receptors and signalling proteins. Fundamental to this line of research is the
exploration of intracellular pathways relevant for disease development.
Proteomics
Proteomic research has added important possibilities to develop disease susceptibility markers and disease progression and intervention tools. Clinical studies To enable clinical studies that require greater power, continuing and promoting collaboration with general hospitals in the region has expanded the recruitment population. To enhance the quality of the collaboration, local physicians in
these hospitals are more involved in the research group and also propose their own studies for discussion in research meetings.
Healthy ageing
“Healthy Aging” has been adopted as the main theme for research and clinical profile of the UMCG. An important longterm project within this theme is “LifeLines” a planned 30-year survey on risk factors (obtained by questionnaire, objective physiological data and biological and genomic markers) for disease development, COPD being one of the leading themes. This fits very well with the research agenda of GRIAC, including co-morbidity and systemic manifestations of COPD. We are and will be actively participating in the development of this programme within the UMCG. In addition, we are participating actively in the development of ERIBA, the programme on aging in the UMCG that is important to both fundamental and clinical research developments.
Publication Report '03