Alejandro Sanchez-Alvarado: The Problem of Regeneration

I. History of Regeneration
II. Principles of Planarian Regeneration
III. Molecular Basis of Regeneration: Planarians as a Model System

Part I: History of Regeneration

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Lecture Overview
Regeneration has fascinated philosophers and scientists since the beginning of history. The wide but uneven distribution of regenerative capacities among multicellular organisms is puzzling, and the permissive/inhibitory mechanisms regulating this attribute in animals remain a mystery. In the first part of this lecture, I will provide a general history of regeneration research from ancient Greece to the beginning of the 20th century. Key concepts will be introduced in their appropriate historical context, and many of the unanswered questions put forward by the problem of regeneration will be discussed. Planarians have attracted the attention of generations of biologists. It is not hard to see why: cut a worm into two fragments and each fragment regenerates a complete organism. Cut it into 8 fragments and each individual fragment will go on to regenerate a complete animal. In this second part of the lecture, I will briefly review the rich history of planarian research, followed by a summary of the central principles of planarian regeneration that have been derived from this extensive, often fascinating body of experimental work. In the third and last part of this lecture, I will introduce the model system we have developed to study animal regeneration, the planarian Schmidtea mediterranea. I will review its anatomy, and the biological attributes that make these animals extraordinarily well suited to dissect the molecular and cellular basis of regeneration. I will also discuss recent work from my laboratory aimed at identifying molecules associated with regenerative capacities.

Speaker Bio
Alejandro Sánchez Alvarado received his Bachelor’s Degree in Molecular Biology and Chemistry from Vanderbilt University in 1986. In 1992, he received his Ph.D. in Pharmacology and Cell Biophysics at the University of Cincinnati School of Medicine, where he studied mouse ES cells and their in vitro differentiation under the tutelage of Dr. Jeffrey Robbins.

In 1994, he joined the laboratory of Dr. Donald D. Brown at the Carnegie Institution of Washington, Department of Embryology as a postdoctoral fellow and in 1995 was appointed Staff Associate. It was during this period that Dr. Sánchez Alvarado began to explore systems in which to molecularly dissect the problem of regeneration.

From 2002-2011 Sánchez Alvarado was a member of the Department of Neurobiology and Anatomy at the University of Utah School of Medicine and in 2005 he was appointed a Howard Hughes Medical Institute Investigator. Sánchez Alvarado moved with his lab to the Stowers Institute for Medical Research in 2011. His current efforts are aimed at elucidating the molecular basis of regeneration using the free-living flatworm Schmidtea mediterranea.

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General Reading
Sánchez Alvarado, A. (2000). Regeneration in the Metazoans: Why does it happen? BioEssays 22, 578-590.

Brockes, J. P., Kumar, A. and Velloso, C. P. (2001). Regeneration as an evolutionary variable. J Anat 199, 3-11.

Reddien, P. W. and Sánchez Alvarado, A. (2004). Fundamentals of Planarian Regeneration. Annu. Rev. Cell Dev. Biol. 20, 725-57.

Sánchez Alvarado, A. (2006). Planarian regeneration: its end is its beginning. Cell 124, 241-5.

Additional Reading
Sánchez Alvarado, A. and Newmark, P. A. (1999). Double-stranded RNA specifically disrupts gene expression during planarian regeneration. Proc Natl Acad Sci U S A 96, 5049-54.

Sánchez Alvarado, A., Newmark, P. A., Robb, S. M. and Juste, R. (2002). The Schmidtea mediterranea database as a molecular resource for studying platyhelminthes, stem cells and regeneration. Development 129, 5659-65.

Newmark, P. A. and Sánchez Alvarado, A. (2000). Bromodeoxyuridine specifically labels the regenerative stem cells of planarians. Dev Biol 220, 142-53.

Reddien, P. W., Bermange, A. L., Murfitt, K. J., Jennings, J. R. and Sánchez Alvarado, A. (2005). Identification of genes needed for regeneration, stem cell function, and tissue homeostasis by systematic gene perturbation in planaria. Dev Cell 8, 635-49.

Reddien, P. W., Oviedo, N. J., Jennings, J. R., Jenkin, J. C. and Sánchez Alvarado, A. (2005). SMEDWI-2 is a PIWI-like protein that regulates planarian stem cells. Science 310, 1327-30.

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