Mike Klymkowsky, Ph.D.

The Sox Axis:  Embryogenesis involves the interplay between maternally established asymmetries and inductive interactions. Our current work focuses on the role of Sox-type transcription factors in these processes and an examination of their evolutionary development.  

The Soxs form are a large and evolutionarily conserved protein family.  We originally became interested in them through their ability of some of them to antagonize β-catenin-mediated Wnt signaling.  

In Xenopus laevis, maternally supplied Sox3 (a B1-type Sox) acts to maintain ectodermal and suppress mesendodermal formation through apparently direct negative regulation of Nodal gene expression and positive effects on genes whose products inhibit Nodal signaling.  Maternally supplied Sox7 (an F-type Sox) is restricted to the vegetal hemisphere of the embryo, and together with zygotically expressed Sox18 (another F-type Sox) induces Nodal expression and is required for cardiovascular and hematopoetic differentiation.

The asymmetry in Sox3 and Sox7 in Xenopus is mirrored by similar asymmetries, particularly in the case of Sox3-like proteins, throughout the metazoans. Together with Dan Meulemans Medeiros in EE Biology, we are examining the role of othologous Soxs in the lamprey, a basal vertebrate.  

Nodal networks and mesoderm-neural crest interactions: Mesoderm is formed through inductive interactions between endoderm and ectoderm, and leads to the generation of a migratory cell population involved in the morphogenic movements of gastrulation.  Later on the neural crest, another migratiory cell population (and referred to as the fourth germ layer of vertebrates) is formed through interactions between mesoderm and neuroectodermal and ectodermal cells.  In our studies, we have found that the zinc-finger transcription factor Slug (Snail2) and the bHLH transcription factor Twist are required for both mesoderm and neural crest formation, as well as cell survival.  Both are regulated, apparently directed by Nodal signaling.  Surprisingly, both Twist and Slug regulate the multifunctional inhibitor of Nodal, BMP, and Wnt signaling, Cerberus. They form a network of interactions that appears to regulate NFkB activity in the early embryo  (Zhang et al, 2006Zhang & Klymkowsky, 2009).  

We are currently using loss of function and RNA rescue to determine where and when mesodermal signals influence the formation, survival, and behavior of the neural crest.  An important part of these studies involves comparing the roles of Slug, Snail, and Twist in Xenopus to their role in another model system, the zebrafish.  These studies are being carried out in collaboration with Kristin Artinger at the Health Sciences Center.

Course & curriculum design and teacher preparation:  Through collaborations with Melanie Cooper (Clemson) on Chemistry, Life, the Universe and Everything and Erin Furtak (School of Education, UC Boulder) on Teaching and Learning Biology  we are studying what and how to teach students the foundational ideas underlying modern biology.  This includes how to apply these ideas to new problems.     

Thinking about biology education:  That education in the biological sciences is currently ineffective (not to mention incoherent) is suggested by the wide-spread support among high school teachers for the teaching of creationism and the popularity of ineffective "alternative therapies" among the general public.  Students are commonly taught to believe in evolutionary processes, rather than understand them.

We have learned much about the conceptual obstacles students face through the development and use of the Biology Concept Inventory (BCI).  The  have built The BCI and the tools used to develop it can be accessed at bioliteracy.net. 

We are also exploring a number of approaches to generate more interactive learning experiences.  These include variations on conventional testing strategies: tutorials and virtual laboratories.  We are currently working on tutorials that address phylogenetic relationships (the tree of life project) and the effects of mutations on phenotype (Thinking like Muller)(watch this space). 

We are part of a vibrant science education community at UC Boulder that includes the Learning Assistant (LA) program, whose goal is to recruit the best students into K-12 teaching and CU Teach, the recruitment and training program for Science and Math teacher certification.