Dr. Michael Layden's interest in biology dates back all the way to his days in high school.
"I remember being really fascinated thinking about how multi-cellularity might have evolved. But as an undergraduate at the University of Rochester, I studied glycosyltransferase enzyme biology in the nematode worm, C. elegans," recalls Dr. Layden.
After graduation, Dr. Layden continued to work in the nematode lab as a laboratory technician, but found that the repetitive scut work of molecular cloning was not very fulfilling, and decided to pursue his graduate studies.
"I went to the University of Oregon for graduate school, where I studied in Chris Doe's lab investigating Drosophila (fruit fly) motor neuron development," explains Dr. Layden. "There I learned how to use genetic approaches to ask questions about gene function during animal development. Through interactions with other faculty members there, my interest in evolution surfaced again."
"By the time I was done with graduate school I knew two things: 1) I wanted to continue studying animal development; 2) I wanted to focus on the nervous system and, in particular, how it evolved."
These questions led Dr. Layden to join the Martindale Lab here at Kewalo. The Martindale lab is well known for its developmental work with the starlet sea anemone, Nematostella vectensis. Dr. Layden recognized that Nematostella is a very good model for studying the evolution of the nervous system as it can regenerate readily, providing the possibility of investigating neurogenesis during both development and regeneration, and because the cnidarians, the group to which Nematostella belongs, evolved before the bilaterians.
"The position of Nematostella before the bilaterians on the tree of life suggests that if you are looking for ancient conserved neurogenic pathways that would help you understand the relationship of nervous systems in the bilaterians, Nematostella is a likely bet as to the place to find them," points out Dr. Layden.
Dr. Layden's research focus in the Martindale Lab has been to establish links at conserved steps in of neural development between Nematostella and other animals. Establishing this conservation is critical because it demonstrates that Nematostella makes neurons in a similar fashion to other animals, and that there must be a core conserved neurogenic mechanism. One gene that has conserved roles in neurogenesis is NvashA, a homolog to achaete-scute class of proneural genes.
In some of his initial experiments on Nematostella, Dr. Layden observed that when he knocked down NvashA function it resulted in a loss of neuronal markers i.e.., proteins expressed specifically in neural cells). Similarly, when he experimentally increased NvashA levels he observed increased neuronal marker expression. Based on these observations, Dr. Layden argues that NvashA promotes neural development in Nematostella. To test this hypothesis, Dr. Layden has been working on identifying potential targets of NvashA using a genome-wide expression microarray. He has found that nearly 400 target genes are turned on by NvashA, and ~80% of them are genes associated with neural biology.
"Currently, I am confirming that these genes are, in fact, targets of NvashA. Then I will have established conservation of NvashA function and identified new neural genes in Nematostella, which can be used to aid further neurogenesis research," explains Dr. Layden.
Most recently, Dr. Layden has been using the workflow he established for NvashA to test other candidate neural genes. In the near future, he would also like to examine the function of NvashA during regeneration, and compare that to its role during normal development.
"Investigating neural regeneration in Nematostella is a unique opportunity for metazoan biology, because most animals that have extensive regenerative capacity often do not produce embryos in the laboratory setting," notes Dr. Layden. "Thus, establishing links and comparing development and regeneration in one species is not easy. However, I believe this is a critical question because though the processes are likely to be mostly similar, the subtle differences are probably critical for proper regeneration and may be candidate pathways for therapies to treat neural degenerative disease and spinal cord injuries in adults."