Major research themes in Duke University’s Developmental and Stem Cell Biology (DSCB) Training Program can be divided into four overlapping, interconnected areas: Mechanisms of Development; Developmental Genetics; Stem Cell Biology and Regeneration; and Evolution and Development.
Mechanisms of Development
Humankind has marveled at the process of embryonic development since at least the age of the ancient Egyptians, 3000 years ago. The rich tradition of descriptive embryology and attendant speculation has been complemented only recently by experimental elucidation of the underlying mechanisms of development. Great strides have been made in fundamental areas such as cell fate determination, body plan establishment, tissue patterning, morphogenesis and organogenesis. Yet as much as we know, it is clear that more remains unknown. For example, we still lack a clear understanding of how vast gene regulatory networks, signaling pathways, micro RNAs, epigenetic regulation and mechanical forces converge to regulate these developmental processes. A technological revolution has resulted in amazing new tools and opportunities to address these critical and exciting areas of research. Duke is a leader in advancing this work.
Incoming graduate students have many opportunities to help reveal the mechanisms underlying development of form and function. DSCB investigators are using state of the art technologies in imaging, bioinformatics, functional genomics, cell labeling, gene manipulation, molecular biology and other approaches in this research. A wide range of model organisms is employed here, to investigate key mechanistic issues in development: intercellular signaling, cellular morphogenesis, gene regulatory networks, patterning, and differentiation of many tissues and organs in multicellular organisms.
Mutations play a critical role in development, often resulting in change that has the potential to alter the health or fitness of an organism. For example, such change can enable useful adaptations to the environment, and ultimately may confer a selective advantage to the mutant’s progeny. On the other hand, a mutation can cause a birth defect, or alter susceptibility to developmental disorders or disease. Several model organisms provide tractable genetic systems that allow genetic loci to be mapped, isolated, identified and manipulated. Experimental exploitation of these features provides an extremely powerful approach to elucidate the underpinnings of normal development and its anomalies.
The major genetic model systems of contemporary developmental biology are fully represented at Duke. DSCB faculty members employ the yeast, Arabidopsis, nematode, fruit fly, zebrafish and mouse systems to determine the genetic and molecular basis of many developmental processes. In addition, several labs are interested in modeling human developmental disease or physiology, using the tools of developmental genetics. The several departments engaged in basic biological science are within steps of the world-renowned Duke Hospital and associated clinical researchers. This proximity creates a rich nexus for collaboration. Duke’s Institute for Genome Science and Policy (www.genome.duke.edu), the Center for Human Genetics (www.chg.duke.edu), and other campus resources further add to the unique training environment in this growing field.
Stem Cells and Regeneration
Development is an ongoing process in humans. Stem cells and other progenitor cells play a crucial role not only in the creation of tissues, but also in their renewal over a lifetime. Thus it is important to understand how adult organs are maintained and replenished during times of health, injury, or advanced age. Stem cells with the capacity to differentiate into more than one cell type are at the heart of the renewal and repair process. Stem cells are typically associated with a local microenvironment, or niche. The niche dynamically integrates signals that stimulate, or in some cases restrain, the self-renewal or differentiation of stem cells. Thus, decisions by uncommitted cells to follow proliferation, patterning, and differentiation signals guide the creation of complex tissues in both embryonic and adult organisms. Elucidation of these signals and niches will yield critical discoveries in the biology underlying stem cells and tissue regeneration. These findings will facilitate not only a better understanding of progenitor cells in normal biology, but also the design of novel strategies for combating disease and disability.
Duke University offers outstanding training opportunities for students interested in the fields of Stem Cell Biology or Regeneration. Program faculty members offer expertise in stem cell biology in many contexts, creating an exciting environment for experimentation and collaboration. Interests of these laboratories include several different kinds of stem cells - neural, hematopoietic, epithelial, and lung – as well as cancer stem cells, germ cells, non-mammalian regeneration and tissue engineering. Students may study stem cell biology in various model systems, including mouse, zebrafish, and flies. Stem cell studies through the DSCB Training Program are complemented by the Stem Cell and Regenerative Medicine Program at Duke. It includes 32 biomedical and bioengineering research laboratories investigating cutting-edge issues in stem cells and regeneration (www.stemcell.duke.edu).
Evolution and Development
With the advent of whole genome sequences from multiple organisms, the shared molecular basis for fundamental developmental mechanisms is more evident than ever. The "toolkit" of development, including transcription factors and signaling systems, is widely shared among eukaryotic organisms. These common features provide a fruitful and exciting means of understanding the genetic and molecular basis for the diversity of life. A prominent research theme in contemporary evolution and development (or "evo-devo") is identifying which genes contributed to developmental differences between species that give rise to distinctive organismal traits. Another important theme in evo-devo is applying a rigorous phylogenetic framework to translating the results of research on the development of model organisms to applications in human health and disease.
Current research in the field of evolution and development integrates the empirical methods of cell biology, molecular biology, and genetics with the computational and analytical frameworks of comparative genomics, molecular evolution, and population genetics. Thus, research in evo-devo can provide training in many methods central to basic and applied research in biology. Exciting opportunities are available at Duke for graduate students interested in pursuing their doctoral research in this field.