Associate Professor Sandra Orgeig

I am a respiratory biologist with a strong focus on the evolution and function of the pulmonary surfactant system. To understand how this complex lipid-protein mixture regulates the surface tension at the air-liquid interface of lungs and promotes efficient lung function, I have taken at times a comparative, an evolutionary as well as a biomedical approach. In the School of Pharmacy & Medical Sciences, I lead a research group in Evolutionary and Functional Molecular Physiology. We use a range of animal models to understand the evolution, development and regulation of molecular systems in the realm of cardio-respiratory physiology. The laboratory’s particular focus has been on the pulmonary surfactant system, but recent work has focused on vascular endothelial growth factors and the process of lymphangiogenesis.

I was originally schooled in Biochemistry at the University of Cape Town, South Africa. After immigrating to Australia in 1990, I completed my PhD in Human Physiology at Flinders University. Since then I have worked in various research fellowship positions at the University of Adelaide, both in Physiology and in Zoology/Environmental Biology before moving to the School of Pharmacy and Medical Sciences in January 2007.

Awards and Fellowships:
Young Tall Poppy Award for South Australia, 2002
Fenner Medal, Australian Academy Science, 2002
ARC Research Fellowship, 1999
ARC Postdoctoral Research Fellowship, 1996

• Biology
• Physiology

PhD (Human Physiology), Flinders University, South Australia, 1994
BSc (Hons) in Biochemistry, University of Cape Town, South Africa, 1988
BSc in Biochemistry, University of Cape Town, South Africa, 1987

• Pulmonary Surfactant
• Surfactant is a complex mixture of lipids and proteins produced by alveolar epithelial cells and secreted into the fluid lining of the lung, where it forms a film at the air-liquid interface. The surfactant film dynamically regulates interfacial surface tension with lung volume to prevent alveolar collapse and reduce the work of breathing. As this critical system develops late during gestation, prematurely-born babies are at risk of developing respiratory distress, a condition often successfully treated with a combination of positive pressure ventilation and/or artificial surfactants. Within the area of pulmonary surfactant, we are interested in environmental and genetic effects on the development of the system as well as on the effect of temperature on the biophysical function of the system.
• Environmental effects on lung and surfactant development
• We are interested in the development of the surfactant system prior to birth/hatching in a variety of animal models, demonstrating different birthing strategies. We are particularly interested in the differences in the timing of development between species that experience different selection pressures (e.g. hypoxia or variable temperatures). We also examine the interplay between genetics and the environment in shaping the development of the fetus and the outcome for the newborn/hatchling. We are also collaborating with the Early Origins of Adult Health Research Group to determine the effects of intrauterine growth restriction (IUGR) on surfactant maturation. Infants that are subjected to IUGR are small at birth and are at an increased risk of developing respiratory distress. We wish to establish the mechanisms and timing of surfactant maturation during late gestation in relation to environmental factors that lead to IUGR, using placentally restricted sheep and undernourished or hypoxia-exposed guinea pigs.
• Effect of temperature on the composition and function of lung surfactant in hibernating and torpid mammals
• Temperature changes can alter the physical state and packing density of the lipids at an air-liquid interface and alter the ability of surfactant to lower surface tension. However, many mammals allow their body temperature to decrease when they enter a reduced metabolic state (e.g. torpor or hibernation) without suffering respiratory distress or surfactant dysfunction. In this project we use biophysical techniques to examine the molecular interactions of lipids and proteins from surfactant isolated from warm and cold mammals (e.g. bats, dunnarts).

• Lizard tail regeneration: a model for investigating lymphangiogenesis
• Impaired lymphatic drainage in upper limbs causes the debilitating swelling termed lymphoedema. Secondary lymphoedema is a frequent side effect of removing axillary lymph nodes and /or adjuvant radiotherapy. Attempts to correct lymphoedema with microsurgical anastomoses of the severed lymph vessels have had limited success to date. However, when composite tissues (flaps) are transferred microsurgically without reconnections of the lymphatics, lymphoedema does not occur because there is lymphatic communication around the periphery of the flap. However, we understand little about the process of lymphangiogenesis because there are no adequate models for exploring the processes involved in the regeneration of lymph vessels. It is now widely recognized that naturally regenerating tissues could provide an alternate approach to embryonic stem cells as models for research into cell differentiation and tissue repair.
• We are currently investigating the physiological and molecular mechanisms underlying the successful regeneration of lymphatic vessels in gecko tails after autotomy. Many lizards have the capacity to drop their tails voluntarily in response to stress or trauma. Termed autotomy, this process results in the fracture of caudal vertebra and cleavage of all tissues including the lymphatics. However, reptilian tail autotomy does not give rise to a lymphoedematous regenerate tail.
• Specifically, we are using nuclear medicine technology, in collaboration with the Nuclear Medicine Department of the Royal Adelaide Hospital, as well as microscopic and immunohistochemical techniques to investigate the structure and function of the regenerating lymphatics. We are also using molecular and proteomic techniques to characterise the reptilian growth factors and receptors, and to examine the molecular control of lymphangiogenesis. This may provide greater insights into the process of lymphoedema and how it can be prevented or treated. In particular we wish to use our understanding of the process of lymph vessel regeneration in the growing tail to gain insights into how we might be able to regenerate lymph vessels in individuals with severe lymph damage.

Selected Reviews

1. Veldhuizen, R., K. Nag, S. Orgeig and F. Possmayer. 1998. The role of lipids in pulmonary surfactant. Biochim. Biophys. Acta 1408:90-108.
2. Daniels, C.B. and S. Orgeig. 2001. The comparative biology of pulmonary surfactant: Past, Present and Future. Comp. Biochem. Physiol. A 129:9-36.
3. Orgeig, S. and C.B. Daniels. 2001. The roles of cholesterol in pulmonary surfactant: Insights from comparative and evolutionary studies. Comp. Biochem. Physiol. A 129:75-89.
4. Orgeig, S., C.B. Daniels, S.D. Johnston and L.C. Sullivan. 2003. Invited Review: The pattern of surfactant cholesterol during vertebrate evolution and development: Does ontogeny recapitulate phylogeny? Reprod. Fert. & Develop. 15:55-73.
5. Daniels, C.B. and S. Orgeig. 2003. Invited Review: Pulmonary surfactant: The key to the evolution of air breathing. News In Physiological Sciences 18: 151-157.
6. Sullivan, L.C., S. Orgeig and C.B. Daniels. 2003. Invited Perspective: The role of extrinsic and intrinsic factors in the evolution of the control of pulmonary surfactant maturation during development in the amniotes. Physiol. Biochem. Zool 76:281-295.
7. Daniels, C.B., S. Orgeig, L.C. Sullivan, N. Ling, M.B. Bennett, S. Schürch, A.L. Val and C.J. Brauner. 2004. The origin and evolution of the surfactant system in fish: Insights into the evolution of lungs and swim bladders. Physiol. Biochem. Zool. 77(5) 732-749.
8. Foot, N.J., S. Orgeig and C.B. Daniels. 2006. The evolution of a physiological system: The pulmonary surfactant system in diving mammals. Respiratory Physiology & Neurobiology 154(1-2):118-38.
9. Orgeig, S., W. Bernhard, S.C. Biswas, C.B. Daniels, S.B. Hall, S.K. Hetz, C.J. Lang, J.N. Maina, A.K. Panda, J. Perez-Gil, F. Possmayer, R.A. Veldhuizen and W. Yan. 2007. The anatomy, physics and physiology of gas exchange surfaces: Is there a universal function for pulmonary surfactant in animal respiratory structures? Integr. Comp. Biol. 47(4): 610-627.

10. Langman, C., S. Orgeig and C.B. Daniels. 1996. Alterations in the composition and function of pulmonary surfactant associated with torpor in a heterothermic mammal (Sminthopsis crassicaudata). Am. J. Physiol. 271:R437-R445.
11. Lopatko, O., S. Orgeig and C.B. Daniels. 1998. Alterations in the surface properties of lung surfactant in the torpid marsupial Sminthopsis crassicaudata. J. Appl. Physiol. 84:146-156.
12. Sullivan, L.C., C.B. Daniels, I.D. Phillips, S. Orgeig and J.A. Whitsett. 1998. Conservation of surfactant protein A: Evidence for a single origin for vertebrate pulmonary surfactant. J. Mol. Evol. 46: 131-138.
13. Johnston, S. D., S. Orgeig, O.V. Lopatko and C. B. Daniels. 2000. Development of the pulmonary surfactant system in two oviparous vertebrates. Am. J. Physiol. (Reg., Int and Comp. Physiol.). 278: R486-R493.
14. Codd, J. R., N.C. Slocombe, C.B. Daniels, P.G. Wood, and S. Orgeig. 2000. Periodic fluctuations in the pulmonary surfactant system in Gould’s wattled bat Chalinolobus gouldii. Physiol. Biochem. Zool. 73:605-612.
15. Ormond, C., C.B. Daniels, and S. Orgeig. 2001. Neurochemical and thermal control of surfactant secretion by alveolar type II cells isolated from the marsupial, Sminthopsis crassicaudata. J. Comp. Physiol. B 171:223-230.
16. Sullivan, L.C. and S. Orgeig. 2001. Dexamethasone and epinephrine stimulate surfactant secretion in type II cells of embryonic chickens. Am. J. Physiol. 281:R770-R777.
17. Codd, J.R., S. Schürch, C.B. Daniels and S. Orgeig. 2002. Torpor-associated fluctuations in surfactant activity in Gould's Wattled Bat. Biochim. Biophys. Acta 1580:57-66.
18. Sullivan, L.C., S. Orgeig, C.B. Daniels. 2002. The control of the development of the pulmonary surfactant system in the saltwater crocodile, Crocodylus porosus. Am. J. Physiol. 283: R1164-R1176.
19. Daniels, C.B., B. Lewis, C. Tsopelas, S. Munns, S. Orgeig, M.E. Baldwin, S.A. Stacker, M.G. Achen, B.E. Chatterton and R.D. Cooter. 2003. Regenerating lizard tails: A new model for investigating lymphangiogenesis. FASEB J. 17: 479-81.
20. Ormond, C.J., S. Orgeig, C.B. Daniels and William K. Milsom. 2003. Thermal acclimation of surfactant secretion and its regulation by adrenergic and cholinergic agonists in type II cells isolated from warm-active and torpid golden-mantled ground squirrels, Spermophilus lateralis. J. Exp. Biol. 206: 3031-3041.
21. Codd, J.R., S. Orgeig, C.B. Daniels and S. Schürch. 2003. Alterations in surface activity of pulmonary surfactant in Gould’s wattled bat during rapid arousal from torpor. Biochem. Biophys. Res. Comm. 308: 463-468.
22. Blacker, H.A., S. Orgeig and C.B. Daniels. 2004. Hypoxic control of the development of the surfactant system in the chicken: Evidence for physiological heterokairy. Am. J. Physiol. 287: R403-R410.
23. Lang, C.J., A.D. Postle, S. Orgeig, F. Possmayer, W. Bernhard, A.K. Panda, K.D. Jürgens, W.K. Milsom, K. Nag and C.B. Daniels. 2005. Dipalmitoylphosphatidylcholine is not the major surfactant phospholipid species in all mammals. Am. J. Physiol. 289: R1426–R1439.
24. Miller, N.J., A.D. Postle, S. Orgeig, G. Koster and C.B. Daniels. 2006. The composition of pulmonary surfactant from diving mammals. Respir. Physiol. Neurobiol. 152:152-68.
25. Miller, N.J., C.B. Daniels, S. Schürch, W.M. Schoel, S. Orgeig. 2006. The surface activity of pulmonary surfactant from diving mammals. Respir. Physiol. Neurobiol. 150: 220-232.
26. Blacker, H.A., C. Tsopelas, S. Orgeig, C.B. Daniels and B.E. Chatterton. 2007. How regenerating lymphatics function: Lessons from lizard tails. Anat. Rec. 290: 108-114.
27. Foot, N.J., S. Orgeig, S. Donnellan, T. Bertozzi and C.B. Daniels. 2007. Positive selection in the N-terminal extramembrane domain of lung surfactant protein C (SP-C) in marine mammals. J. Mol. Evol. 65(1):12-22.
28. Potter, S., S. Orgeig, S. Donnellan and C.B. Daniels. 2007. Purifying selection drives the evolution of surfactant protein C (SP-C) independently of body temperature regulation in mammals. Comp. Biochem. Physiol. D - Genomics & Proteomics 2(2): 165-176.
29. Bernhard, W., A. Schmiedl, G. Koster, S. Orgeig, C. Acevedo, C.F. Poets, A.D. Postle. 2007. Developmental changes in rat surfactant lipidomics in the context of species variability. Pediatr. Pulmonol. 42(9):794-804.