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Michael H. Irwin, PhD

Dr. Michael H. Irwin, Research Associate Professor in the Department of Pathobiology, earned a doctorate in Cell Biology and Anatomy at the University of Alabama at Birmingham in 1987.  He was awarded a postdoctoral fellowship from the American Heart Association Alabama Affiliate to study the molecular arrangement of laminin in glomerular basement membranes in the laboratory of Dale Abrahamson at UAB.  He then worked as a Research Associate in the laboratory of Eldon Geisert at UAB, characterizing a cell adhesion molecule, present on reactive astrocytes, that plays a role in scar formation after CNS injury.  In 1993, he became involved in the Transgenic Animal/Embryonic Stem Cell Resource initially as a Research Associate then promoted to Associate Director of the University-wide core facility in 1999.  He came to Auburn University in 2006 to direct the Auburn Univrsity Transgenic Facility and continue studies with Dr. Carl A. Pinkert on transmitochondrial animal modeling.
334-844-5580
mhi0001@auburn.edu

Research Interests

Mitochondrial medicine is an emerging area of research. This field has rapidly developed following the description in the late 1980s of the first mitochondrial mutations that led to human disease. However, through the late 1990s, in vivo animal models were extremely rare and limited to characterizations of spontaneous mutations.

My interests relate to the technical hurdles associated with creating transmitochondrial research animals; i.e., animals harboring engineered mutations in the mitochondrial genome.  Though the mitochondrial genome is small (16.6kb in vertebrates), transfection of mitochondrial DNA (mtDNA) or entire mitochondrial genomes into mitochondria is not possible by conventional transgenesis.   Furthermore, recombination within mitochondria is a rare event, such that harnessing the mitochondrial recombination machinery is not possible.  

To address these issues, our laboratory has utilized a mtDNA large-scale deletion mutation that is small enough to electroporate into isolated mouse mitochondria without causing irreparable damage to the mitochondrial membranes.  These transfected mitochondria can then be microinjected into fertilized eggs for production of heteroplasmic mice (mice harboring both wild type and mutated mtDNA) that may serve as an animal model for a similar class of large-scale deletions seen in human patients.  

A related project seeks to explore new strategies for introducing isolated, genetically manipulated mitochondria into embryonic stem cells via liposome encapsulation and subsequent fusion of liposome vesicles with the ES cell plasma membrane.  Going forward, development of strategies for increasing mtDNA recombination frequency would enable techniques for introducing specific point mutations, allowing for the creation of mouse models for a variety of human diseases of the mtDNA.

In addition to my own research, interactive studies in animal transgenesis through the Auburn University Transgenic Facility are envisioned across a broad spectrum of interests in the life sciences at Auburn University. 

Selected Publications

Pinkert, C.A., M.H. Irwin and R.J. Moffatt. 1995. Transgenic animal technology.  In: R.A. Meyers (Ed.) Encyclopedia of Molecular Biology. VCH, New York.

Pinkert, C.A., M.H. Irwin and R.J. Moffatt.  1995. Transgenic animal modeling.  In: R.A. Meyers (Ed.) Molecular Biology and Biotechnology.  pp. 901-907, VCH, New York.

Geisert, E.E., L. Yang and M.H. Irwin.  1996.  Astrocyte growth, reactivity and the target of the antiproliferative antibody, TAPA.  J. Neuroscience 16(17):5478-5487. 

Irwin, M.H., R.J. Moffatt and C.A. Pinkert. 1996. Identification of transgenic mice by PCR analysis of saliva. Nature Biotechnol. 14:1146-9.

Vergara, G.J., M.H. Irwin, R.J. Moffatt and C.A. Pinkert. 1997. In vitro fertilization in mice: strain differences in response to superovulation protocols and effect of cumulus cell removal. Theriogenology 47:1245-52.

Pinkert, C.A., M.H. Irwin and R.J. Moffatt. 1997. Transgenic animal modeling. In: R.A. Meyers (Ed.) Encyclopedia of Molecular Biology and Molecular Medicine. Volume 6, pp. 63-74, VCH, New York.

Pinkert, C.A., M.H. Irwin, L.W. Johnson and R.J. Moffatt. 1997. Mitochondria transfer into mouse ova by microinjection. Transgenic Res. 6:379-83.

Irwin, M.H., L.W. Johnson and C.A. Pinkert. 1999. Isolation and microinjection of somatic cell-derived mitochondria and germline heteroplasmy in transmitochondrial mice. Transgenic Res. 8:119-23.

Pinkert, C.A., L.W. Johnson, M.H. Irwin, S. Wong, E.E. Baetge, D.F. Wolfe, S.A. Simpkins, W.F. Owsley and F.F. Bartol. 2001. Optimization of superovulation and fertilization protocols in the production of transgenic swine. Adv. Reprod. 5:45-53.

Irwin, M.H., V. Parrino and C.A. Pinkert. 2001. Construction of a mutated mtDNA genome and transfection into isolated mitochondria by electroporation.   Adv. Reprod. 5:59-66.

Irwin, M.H., W.K. Pogozelski and C.A. Pinkert. 2002. PCR optimization for detection of transgene integration. In: C.A. Pinkert (Ed.) Transgenic Animal Technology: A Laboratory Handbook. 2nd ed., pp. 475-84. Academic Press, San Diego.

Pinkert, C.A., M.H. Irwin and R.L. Howell. 2004. Animal biotechnology and modeling. In: R.A. Meyers (Ed.) Encyclopedia of Molecular Cell Biology and Molecular Medicine. Vol. 1, pp. 209-40. Wiley-VCH, Weinheim.

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