Top: Nuclei (green) and neuronal synapses (red) seen with fluorescence.Bottom: C. elegans hermaphrodite in white light (adult length 1.5 mm).
Research Background
The research in our laboratory uses a model organism, the small soil nematode Caenorhabditis elegans , to examine the development and function of the nervous system. C. elegans is a very simple animal: the adult hermaphrodite has exactly 302 identified, invariant neurons. C. elegans are small (1 mm long), transparent, have a relatively small genome, and are quick and easy to grow. There are thousands of mutants and transgenic animals that we can use to study the roles of specific genes and proteins in the nervous system and behavior. Therefore, we can use molecular biology, genetics, cell biology, and behavioral assays to examine the development, distribution, and function of genes and proteins in specific cells and circuits and behaviors.
Current Research Topic I
We are studying the regulation of neuronal development and function by the monoamine (MA) neurotransmitters dopamine and serotonin. Many drugs, prescribed or abused, act by interfering with normal functioning of monoamines (MAs). The proteins that are targets of these drugs are similar in humans and simple animals like C. elegans . For example, dopamine and serotonin modulate neuronal activity to regulate movement, satiety, and aging.
Mutants that alter MA signaling are relatively healthy, as shown in a video (made by two undergraduate researchers in the lab) of mutants with defects in serotonin and/or dopamine signaling.
Since mutants are viable, we can study mutants with defects in multiple genes that regulate monoamines synthesis, transport, and reception to understand more about MAs in all animals.
Our questions on MAs include:
- How do acute and chronic changes in MA genes affect development, behavior, and drug sensitivity?
- How does monoamine oxidase (MAO) affect MA degradation in C. elegans ?
- What are the targets of prescribed inhibitors of MAO (MAOIs) in normal vs. mutant C. elegans ?
Current Research Topic II
Scientist have recently discovered that epigenetic regulation, that is, regulation of gene expression without alterations in the DNA, is very important. One form of epigenetic regulation is post-translational modification of the histones around which DNA is wrapped. We are studying a specific histone demethylase called AMX1 that is expressed in a subset of neurons in the head.
Our questions on AMX1 include:
- What are the enzymatic activities of this protein in vitro ?
- Where is AMX1 expressed under different developmental conditions?
- How does AMX1 affect neuronal function, behavior, and development?
Our goal is to understand a piece of the puzzle of how genes and proteins in the nervous system control the development and behavior of this very simple animal. Since the genes we study are evolutionarily conserved in humans, the understanding that we gain will inform our understanding of the 100 billion neurons present in our brains.