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Welcome to the Haller Lab: RESPIRATORY CELL PHYSIOLOGY

 

 

General

Initially, we focused on Ca2+-stores and -signalling in various epithelial cells and introduced, for example, GPN as a selective agent to discharge endo-lysosomal Ca2+ revealing some novel aspects in intracellular Ca2+ sequestration and -homeostasis (Haller et al. Cell Calcium 1996). Our group then moved for many years towards regulatory aspects of surfactant secretion by lung alveolar type II cells (Haller et al. PNAS 1999) and towards the significance and biophysical properties of pulmonary surfactant at the respiratory air-liquid interface (Ravasio et al. J. Biol. Chem. 2010). General mechanisms of exocytosis were always at the forefront of our research (Frick et al. Am. J. Respir. Cell Mol. Biol. 2001) as it was alveolar epithelial cell physiology in general (Dietl & Haller; Annu. Rev. Physiol. 2005).
We used and adapted many optical and fluorescence techniques like FRAP, flash photolysis, laser tweezers or interferometry in conjunction with AFM, EM or SEM, and implemented others like an equibiaxial stretch device to mimic lung distension, an inverted air-liquid interface to simulate the alveolar microenvironment, or polarization microscopy to investigate intracellular lipid organisation. These studies led to several new insights into alveolar biology, some of which summarized by own or external reviews (Possmayer et al. Respir. Physiol. Neurobiol. 2010). They will be completed by investigations on vectorial drug transport and drug sequestration by lung alveolar type II cells. The outcome could possibly move the lung into a new perspective as an excretory organ for highly lipophilic compounds but also as a prime target for a distinct class of drugs and pharmaceuticals.

 

Cellular mechanisms of exocytosis (e.g. T. Haller, J. Ortmayr, F. Friedrich, H. Völkl, P. Dietl, 1998: Proc. Natl. Acad. Sci. USA 95: 1579-1584)

Official logo of the 2002 FASEB Summer Research Conference on Lung Surfactant in Vermont, USA. Logo adapted from a confocal image of a single ATII cell caught in the process of surfactant exocytosis, published in: Mair et al. Am. J. Physiol. 1999

 

Current work has also started to include O2 transport by red blood cells with special emphasis on the role of hemoglobin in modulating O2 transfer in the human body. In this respect we are investigating novel aspects of O2transport in relation to high altitude, accidental hypoxemia, relevant clinical interventions and pharmacological modulations (see latest Publications). Future projects will aim to implement newly developed methods for oxygen dissociation measurements (Woyke et al. Physiol. Rep. 2021) as a routine analytical service in everyday clinical practice.

 

Press

Die Presse
Science ORF
Eurac Research Magazine
Top Tirol (117-119)
Tiroler Tageszeitung
Innovations report

 

MyPoint

CAST Life Science Business Award
LB explosionen
Ambroxol
Laser Tweezers
Oxygen dissociation curve

 

Videos

Ambroxol
Oxygen dissociation curve measurement
Blood sampling with kissing bugs
Fusion activated Ca2+ entry
Lamellar bodies at air-liquid interfaces
Laser Tweezers

 

Techniques

„The bricoleur… is someone who uses the means at hand, that is, the instruments he finds at his disposition around him, those which are already there… for an operation for which one tries by trial and error to adapt them, not hesitating to change them whenever it appears necessary”

 Jacques Derrida about the bricoleur in Claude Lévi-Strauss: The Savage Mind

 Our ‘Bricolage’ is essentially based on standard laboratory methods with an accent on primary cell culture and fluorescent microscopy. Though, we are constantly in search of innovative strategies to tackle the problems associated with the lung’s complex microenvironment, not only comprising oscillating tissue stretch and strain but also tensile forces acting on the highly curved and dynamic air-liquid interfaces and transmitted to the cells. So, for example, we have introduced:

  • a modified Du Noüy vertical pull surface tension technique (T. Haller et al. J. Physiol. Lung Cell. Mol. Physiol.286: L1009-1015, 2004)
  • a non-invasive optical surface tensiometry (C. Bertocchi et al. J. 89: 1353-61, 2005)
  • a miniaturized inverted air-liquid interface device (T. Haller et al. J. Physiol. Lung Cell. Mol. Physiol. 286: L1009-1015, 2004)
  • a fluorescence microplate-based exocytosis assay (A. Wemhöner et al. Biomol. Screen. 11: 286-295, 2006)
  • a high throughput lipid adsorption assay (Ravasio et al. Lipid Res. 49: 2479-88, 2008)
  • an equibiaxial cell-strain device (M. Frick et al. J. Physiol. Lung Cell. Mol. Physiol. 286: L210-220, 2004)
  • a hemoglobin-oxygen dissociation assay (Woyke et al. Rep. 2021 Aug;9(16): e149959

Some of the above and other, non-published ideas led to patent applications whereas other inventory work advanced towards market maturability (Haller et al. Anal. Biochem. 1994). A recent MUI patent specification on a gas perfusion measuring device resulted in an international PCT application (PCT/EP2021/079295). For very specific problems we also used captive bubble and Wilhelmy surface balance measurements beside some other, non-routine technologies. Currently, we are also exploiting the possibilities of confocal CARS and polarization microscopy and are working on the refinement of cell culture conditions to better simulate all aspects of the alveolar condition.

Cellular mechanisms of exocytosis (e.g. T. Haller, J. Ortmayr, F. Friedrich, H. Völkl, P. Dietl, 1998: Proc. Natl. Acad. Sci. USA 95: 1579-1584)

Bricolage in action: Dr. Simon Woyke (see Team) assembling leftovers from the refurbishment of the old Fritz-Pregl-Str. 3 building for the use in the 3H ODC trial (hypoxia, hypercapnia, hypothermia) on avalanche burials, performed in collaboration with Eurac Research, Bolzano

 

 

 

Publication highlights

Selected from different areas of research, and based on citations well above 100 (according to Google scholar 10/2022):

 Dynamics of surfactant release in alveolar type II cells. Haller, T., Ortmayr, J., Friedrich, F., Volkl, H., and Dietl, P. Proc: Natl: Acad: Sci. U. S. A. 95, 1998, 1579-1584 http://www.ncbi.nlm.nih.gov/pubmed/9465058 Citations: 157

 The lysosomal compartment as intracellular calcium store in MDCK cells: a possible involvement in InsP3-mediated Ca2+ release. Haller, T., Dietl, P., Deetjen, P., and Völkl, H. Cell calcium 19, 1996, 157-165 http://www.ncbi.nlm.nih.gov/pubmed/8689673 Citations: 135

 A respirometer for investigating oxidative cell metabolism: toward optimization of respiratory studies. Haller, T., Ortner, M., and Gnaiger, E.Anal. Biochem. 218, 1994, 338-342 http://www.ncbi.nlm.nih.gov/pubmed/8074290 Citations: 126

 

On the cover, featured articles, textbook entry

 

Latest publications (from 2020)

2022: The effect of desflurane, isoflurane and sevoflurane on the hemoglobin oxygen dissociation curve in human blood samples. Ronzani, M., Woyke, S., Mair, N., Gatterer, H., Oberacher, H., Plunser, D., Haller, T., Ströhle, M., Ruegg, C. Sci. Rep. Aug 10;12(1):13633. doi: 10.1038/s41598-022-17789-6

 2022: The Impact of nebulized epoprostenol and iloprost on hemoglobin oxygen affinity: an ex vivo experiment. Woyke, S., Mair, N., Haller, T., Ronzani, M., Plunser, D., Oberacher, H., Gatterer, H., Ruegg, C., Ströhle, M. Am. J. Physiol. Lung Cell. Mol. Physiol. 322: L898-L903. doi: 10.1152/ajplung.00084.2022

 2022: Effects of Carbon Dioxide and Temperature on the Oxygen-Hemoglobin Dissociation Curve of Human Blood: Implications for Avalanche Victims. Woyke, S., Brugger, H., Ströhle, M., Haller, T., Gatterer, H., Dal Cappello, T., Strapazzon, G. Front. Med. 8:808025. doi: 10.3389/fmed.2021.808025

 2021: Dose-and Sex-Dependent Changes in Hemoglobin Oxygen Affinity by the Micronutrient 5-Hydroxymethylfurfural and α-Ketoglutaric Acid. Woyke, S., Mair, N., Ortner, A., Haller, T., Ronzani, M., Rugg, C., Ströhle, M., Wintersteiger, R., Gatterer, H. Nutrients 13(10). doi: 10.3390/nu13103448

2021: High‐throughput determination of oxygen dissociation curves in a microplate reader—A novel, quantitative approach. Woyke, S., Ströhle, M., Brugger, H., Strapazzon, G., Gatterer, H., Mair, N., Haller, T. Physiological Reports 9(16). doi: 10.14814/phy2.14995

 2021: Stimulation of surfactant exocytosis in primary alveolar type II cells by A. fumigatus. Schiefermeier-Mach, N., Perkhofer, S., Heinrich, L., Haller, T. Med. Mycol. 59(2). doi: 10.1093/mmy/myaa042

 2020: Migrating lung monocytes internalize and inhibit growth of Aspergillus fumigatus conidia.Schiefermeier-Mach, N., Haller, T., Geley, S., Perkhofer, S. Pathogens 9(12). doi: 10.3390/pathogens9120983

 2020: tBHP treatment as a model for cellular senescence and pollution-induced skin aging. Wedel, S., Martic, I., Hrapovic, N., Fabre, S., Madreiter-Sokolowski, CT., Haller, T., Pierer, G., Ploner, C., Jansen-Dürr, P., Cavinato, M. Mech. Ageing Dev. 190. doi: 10.1016/j.mad.2020.111318

»more

(For a comprehensive list please visit Google Scholar, ORCID or Reserach Gate)

 

Current international collaborations

University of Ulm, Institute of General Physiology
Universidad Complutense Madrid, Department of Biochemistry
Eurac Research, Institute of Mountain Emergency Medicine
Renal Research Institute, New York