Skip to main content
Sign In
 

Bates Lab


Dr. Emily Bates uses genetics to determine the molecular mechanisms of pediatric disorders. Research in her lab has identified the mechanism by which mutations that disrupt an ion channel lead to cleft palate, a likely target for alcohol that causes Fetal Alcohol Syndrome, and a mechanism by which mutations in a tubulin gene disrupt brain development.


Mechanisms of Disease

Clues into common pathology can start from human genetic disorders. As the first step to finding potential therapeutics, Dr. Emily Bates uses genetics to determine molecular mechanisms of pediatric disorders.


Ion Channels in Morphological Development
The Bates lab identified a potential therapeutic target for fetal alcohol syndrome by studying a rare genetic disorder that has the same spectrum of congenital birth defects as FASD. The genetic disorder, (Andersen Tawil Syndrome) is caused by genetic disruption of a potassium channel. This potassium channel is blocked in the presence alcohol. Research in the Bates lab has determined that this potassium channel is needed for canonical Bone Morphogenetic Protein (BMP) signaling from flies to mice. We now use both flies and mice to determine which ion channels contribute to developmental signaling.

This is exciting because ion channels are readily targeted pharmacologically. This presents the possibility that ion channels could be manipulated to influence cell fate choices to generate specific tissues like cartilage or bone. For these potential applications, the Bates lab explores the role of ion flux in development.


Cytoskeleton in Brain Development
Cells require a cytoskeleton to be drastically remodeled during development, but stable in adulthood. An extreme example of the profound changes required of the cytoskeleton is neuronal migration and axonogenesis. We use mutations that disrupt components of the cytoskeleton to understand how cytoskeleton function impacts brain development. Specifically, we model mutations that were derived from patients with developmental brain disorders in rodent neurons to understand how the mutations impact morphology of a neuron, the dynamic changes in the cytoskeleton, and ultimately the structure of the brain.

We recently used a multi-system approach to show that a mutation in mouse Tuba1a (Tuba1aND) destabilizes the αβ heterodimer to disrupt the normal blend of tubulin isotypes, leading to defects in cortical layering and innervation of limbs (Hansen et al, 2016). Neurons in Tuba1aND embryos exhibit specific defects in axon architecture, including delayed axon extension and changes in tubulin posttranslational modifications in the growth cone. These mice also have adult onset ataxia and motor deficits showing that Tuba1a is important for post-natal brain function. Our results point to an important role for TUBA1A in the axon, and we are now poised to elucidate the underlying mechanism and whether this mechanism depends on unique coding or non-coding features of this α-tubulin isotype. Our goal is to understand how the cytoskeleton is regulated to form specific cellular structures and perform specific functions in neurons.



DahalGiri 206 x 156.jpg Jayne Aiken, PhD candidate
Research Project: Using Tubulinopathy patient mutations to understand how microtubules contribute to neuronal architecture and brain development.
RoseSteven 206 x 156.jpg Georgia Buscaglia, PhD candidate
Research project: Elucidating the role of a brain specific tubulin, Tuba1a in neuronal function and development.



Alumni
DahalGiri 206 x 156.jpg Giri Dahal, PhD, Postdoctoral Fellow
Research Project:  Mechanisms underlying Andersen-Tawil Syndrome and the developmental function of a potassium channel.
RoseSteven 206 x 156.jpg Steven Rose, BS, Research Assistant
​​​​​​​​

Dahal, Giri, Pradhan, Bates, EA, Inwardly Rectifying Potassium Channels influences Drosophila wing morphogenesis by regulating Dpp release, Development 2017, Aug. 1; 144(15):2771-2783. Doi: 10.1242/dev.146647. PMID: 28684627

Belus, Matthew, Madison Rogers, Alladdin Elzubier, Josey, Megan, Rose, Steven, Bates, EA; Kir2.1 is important for BMP signaling to correctly pattern the mammalian face, Developmental BiologyPMID: 29571612 DOI:10.1016/j.ydbio.2018.02.012

Bates, EA; A potential molecular target for morphological defects of fetal alcohol syndrome: Kir2.1; Current Opinion in Genet Dev, 2013 Jun;23(3): 324-99 doi:10.1016/j.gde.2013.05.001. Epub 2013 Jun 4.

Bates, EA: Ion channels in Development and Cancer, Annual Review of Cell and Developmental Biology, 2015; 31:231-47. doi :10.1146/annurev-cellbio-100814-125338

Aiken, Jayne, Buscaglia, Georgia, Bates, EA, Moore, J; The alpha tubulin gene TUBA1A in brain development: a key ingredient in the neuronal isotype blend, Developmental Biology, 2017 doi: 10.3390/jdb5030008.

Link to publications on PubMed:
https://www.ncbi.nlm.nih.gov/sites/myncbi/1hoogBcU4sYQa/bibliography/47992690/public/?sort=date&direction=ascending​

​​

Bates Lab
University of Colorado Denver
RC1 North, 4th Floor, Room 4134
12800 E. 19th Avenue, Mailbox 8313
Aurora, CO  80045
Phone: 303-724-8303
Email: emily.bates@ucdenver.edu