Fruit Flies, Drosophila melanogaster

Research Overview, Projects & Collaborators

tl;dr version - we try to figure out how the cells in your brain work, but please, read on!

The central questions that guide research in the lab are: How do neurons function; how do they develop and how do function and development influence each other? We are motivated to study these questions to better understand how the nervous system and the brain give rise to behaviors in both health and disease.

What are synapses? They are the very small and very close connections between nerve cells and the target cells the neurons are communicating with, usually other neurons but also muscle and glands. Synapses are the point of information transfer in neural circuits and are critically important for all neural and brain function. There are probably 100 trillion synapses in a human brain and just reading this page you are using a lot of them!

For many reasons, our main study system is the fruit fly, Drosophila melanogaster. Famous for its long history of classical genetics and now even more-so for its molecular genetic tools, Drosophila also provide an amazing system for studying synaptic transmission and the development of synapses. Despite being a 'simpler' organism, flies show amazingly complex behaviour, such as learning, memory, & agression and we know that at the genetic level, there is a high degree of similarity in fly and human genes. Information we generate studying flies can be translated to a more general understanding of how neurons develop and function. We have more recently been using cell culture systems to conduct specific analysis of sub-cellular protein trafficking.

The main technical approaches we use are genetics, electrophysiology of synaptic transmission, a variety of imaging technologies, including confocal, live-cell imaging, electron microscopy and non-linear microscopy. We also do some molecular biology and biochemistry from time-to-time depending on the project requirements.

Projects

The Publications page links to some of our recent papers and provides links to all of the papers published from the lab. The main Projects we are working on right now include:

1. Analyzing the contribution of synaptic scaffolding proteins to synaptic development and function. Led by Dr. Katie Harris, along with recent MSc graduate Ashley Hogg, the project is focusing on the role Shank plays to properly establish synaptic connections and examining what happens to synaptic transmission when Shank is genetically modified. This project was started by Katie when she was a Postdoctoral Fellow at M.I.T with Dr. J. Troy Littleton

2. A longstanding project on the role of NSF in synaptic function and development. We discovered quite unexpectedly that down-regulating NSF activity leads to a dramatic overgrowth of the neuromuscular junction. PhD student Christine Nguyen is studying the effects of genes that interact with the NSF phenotypes to bring further understanding to its role in synaptic function and development.

3. Can we re-create the nerve muscle junction in culture? Christine Nguyen is collaborating with The Gilbert Lab to grow motor nerves and muscle in cultures from stem cells. Her role will be conduct a physiological analysis of the electrical properties of the muscle and characterize synaptic transmission in cultures derived from normal and diseased patients.

4. What are the effects of alcohol on the developing nervous system? Recent MSc student Gordana Scepanovic led a project to determine if Drosophila can be used as a model to understand what happens to neural development following brief exposure to alcohol very early in their life.

5. Technological advances are often important for advancing knowledge and we are collaborating with the Barzda Lab to image biological tissue with non-linear microscopy. These instruments are not commercially available and we have been at the forefront of applying this technology to imaging muscle structure and eye development. PhD student Abi Karunendiran is leading these projects and is currently refining our ability to conduct live imaging of skeletal, visceral and cardiac muscle with second-harmonic generation microscopy.

J. Troy Littleton, Massachusetts Institute of Technology

Littleton Lab

Analyzing the role of postsynaptic scaffolding and intracellular trafficking in synapse development and function