Dr Pika Miklavc
Lecturer in Human Physiology
I studied Biology on University of Ljubljana in Slovenia and continued there as a PhD student in the Department of Biology. During my graduate studies I investigated olfactory coding in fish and obtained my PhD in 2005. I then became interested in cellular mechanisms of secretion and moved to Ulm University in Germany as a Marie Curie Fellow of the European Commission in the Research Training Network Pulmonet. There I explored different stages in secretion of lung surfactant, using high-resolution microscopy techniques.
After conclusion of the Pulmonet programme I continued working in the Medical School of the Ulm University as university assistant in the Institute of General Physiology. In 2013 I acquired Margarete von Wrangell Fellowship from the Ministry of Science, Research and the Arts of the Land Baden-Württemberg. With help of this fellowship I obtained a Habilitation in Physiology, which is a German post-doctoral qualification for teaching in Higher Education. In 2016 I was appointed as Lecturer in Human Physiology on University of Salford.
I teach physiology and pathophysiology for students in Biology and Biomedicine Programmes. In year 2017/18 I am a module leader for Biological Skills, where I deliver practical courses on histology and microscopy. I participate in Study Skills module for level 4 students and in final year project delivery for level 6 students.
My previous teaching experience includes teaching physiology to students of Medicine, Dental Medicine and Molecular Medicine.
My research focuses on secretory processes in lung epithelial cells. Secretion has a central role in lung physiology and pathophysiology. Secretory cells in the airways release mucins, which help to keep the lungs free of pathogens. In contrast, secretory type II cells of lung alveoli secrete lipo-protein surfactant, which reduces surface tension of the alveolar lining fluid and enables inspiration. These secretory cells use regulated exocytosis, a specialized intracellular vesicular transport process, to release substances in the extracellular space. Secretory materials are stored in intracellular vesicles, which fuse with the plasma membrane upon appropriate stimulation.
Alveolar type II cells have large secretory vesicles and a particularly slow, sequential fusion process, which makes them an ideal cell model to study single vesicle fusion events in living cells using high-resolution microscopy methods. My research encompasses different stages of exocytosis, with focus on regulation of vesicle content release after fusion pore opening. Especially in the late stages of exocytosis actin cytoskeleton and calcium ions play a pivotal role for exocytosis of large secretory vesicles and secretion of poorly soluble substances. Secretory vesicles in type II cells acquire actin coats after fusion with the plasma membrane. The compression of these coats provides mechanical force to enable surfactant release. In addition, influx of calcium through P2X4 channels localized on surfactant-containing secretory vesicles contributes to fusion pore dilation and efficient surfactant extrusion.
In addition to investigating basic mechanisms of secretion I am interested in pathological alterations of the secretory mechanisms in lung cells and their implications for lung function. As an example, it is becoming increasingly evident that surfactant deficiency or dysfunction is involved in a range of lung disorders. Deficient surfactant synthesis in prematurely born infants can result in the infant respiratory distress syndrome (IRDS). In adults, surfactant deficit can lead to pulmonary fibrosis, a poorly understood condition which affects a significant percentage of population and irreparably damages lung tissue.
Qualifications and Memberships
PhD on University of Ljubljana, Slovenia. Title of the thesis: Behavioural discrimination of amino acids in zebrafish (Danio rerio). 2005.
Habilitation on Ulm University, Germany. Title of the thesis: Regulation of hemifusion and post-fusion phase of exocytosis in alveolar type II cells. 2015.
Membership: The Physiological Society
Hobi N, Giolai M, Olmeda B, Miklavc P, Felder E, Walther P, Dietl P, Frick M, Perez-Gil J, Haller T. 2016. A small key unlocks a heavy door: The essential function of the small hydrophobic proteins SP-B and SP-C to trigger adsorption of pulmonary surfactant lamellar bodies Biochim Biophys Acta, 1863(8): 2124-34
Kittelberger N, Breunig M, Martin R, Knölker HJ, Miklavc P. 2016. The role of myosin 1c and myosin 1b for surfactant exocytosis. J Cell Sci, 129: 1685-1696
Fois G, Hobi N, Felder E, Ziegler A, Miklavc P, Walther P, Radermacher P, Haller T, Dietl P. 2015. A new role for an old drug: Ambroxol triggers lysosomal exocytosis via pH-dependent Ca2+ release from acidic Ca2+ stores. Cell calcium, 58(6): 628-37
Miklavc P, Ehinger K, Sultan A, Felder T, Paul P, Gottschalk K-E, Frick M. 2015. Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles. J Cell Sci, 128(6): 1193-203
Miklavc P, Ehinger K, Thompson KE, Hobi N, Shimshek DR, Frick M. 2014. Surfactant secretion in LRRK2 knock-out rats: changes in lamellar body morphology and rate of exocytosis. PLoS ONE, 9(1): 1-10
Miklavc P, Thompson KE, Frick M. 2013. A new role for P2X4 receptors as modulators of lung surfactant secretion. Front Cell Neurosci, 7:171
Miklavc P, Hecht E, Hobi N, Wittekindt OH, Dietl P, Kranz C, Frick M. 2012. Actin coating and compression of fused secretory vesicles are essential for surfactant secretion: a role for Rho, formins and myosin II. J Cell Sci, 125(Pt 11): 2765-74
Fois G, Wittekindt O, Zheng X, Felder ET, Miklavc P, Frick M, Dietl P, Felder E. 2012. An ultra fast detection method reveals strain-induced Ca(2+) entry via TRPV2 in alveolar type II cells. Biomech Model Mechanobiol, 11(7):959-71
Usmani SM, von Einem J, Frick M, Miklavc P, Mayenburg M, Husmann M, Dietl P, Wittekindt OH. 2012. Molecular basis of early epithelial response to streptococcal exotoxin: role of STIM1 and Orai1 proteins. Cell Microbiol, 14(3):299-315
Miklavc P, Valentincic T. 2012. Chemotopy of amino acids on the olfactory bulb predicts olfactory discrimination capabilities of zebrafish Danio rerio. Chem Senses, 37(1):65-75.
Miklavc P, Frick M. 2011. Vesicular calcium channels as regulators of the exocytotic post-fusion phase. Commun Integr Biol, 4(6):796-8.
Miklavc P, Mair N, Wittekindt OH, Haller T, Dietl P, Felder E, Timmler M, Frick M. 2011. Fusion-activated Ca2+ entry via vesicular P2X4 receptors promotes fusion pore opening and exocytotic content release in pneumocytes. Proc Natl Acad Sci USA, 108(35):14503-8.
Valentincic T, Miklavc P, Kralj S, Zgonik V. 2011. Olfactory discrimination of complex mixtures of amino acids by the black bullhead Ameiurus melas. J Fish Biol, 79(1):33-52
Dietl P, Liss B, Felder E, Miklavc P, Wirtz H. 2010. Lamellar body exocytosis by cell stretch or purinergic stimulation: possible physiological roles, messengers and mechanisms. Cell Physiol Biochem, 25(1): 1-12
Miklavc P, Frick M, Wittekindt OH, Haller T, Dietl P. 2010. Fusion-activated Ca2+ entry: an “active zone” of elevated Ca2+ during the postfusion stage of lamellar body exocytosis in rat type II pneumocytes. PLoS ONE, 5(6):1-10
Miklavc P, Albrecht S, Wittekindt OH, Schullian P, Haller T, Dietl P. 2009. Existence of exocytotic hemifusion intermediates with a lifetime up to seconds in type II pneumocytes. Biochem J, 424(1): 7-14
Miklavc P, Wittekindt OH, Felder E, Dietl P. 2009. Ca2+-dependent actin coating of lamellar bodies after exocytotic fusion: a prerequisite for content release or kiss-and-run. Ann NY Acad Sci, 1152:43-52.
Felder E, Siebenbrunner M, Busch T, Fois G, Miklavc P, Walther P, Dietl P. 2008. Mechanical strain of alveolar type II cells in culture: changes in the transcellular cytokeratin network and adaptations. Am J Physiol Lung Cell Mol Physiol, 295(5):L849-57
Valentincic T, Miklavc P, Dolenšek J, Pliberšek K. 2004. Correlations between olfactory discrimination, olfactory receptor neuron responses, and chemotopy of amino acids in fishes. Chem Senses, 29: i312-i314