- Home
- Academic Staff
- Dr Sean Millard
Dr Sean Millard
 |
Position
Lecturer in Physiology
Qualifications and Awards
PhD Molecular Biology 2001
Affiliations
Queensland Brain Insitute
Associations
Australian Neuroscience Society
Contact Details
| Location | Room 520,Otto Hirschfeld Building 81, St Lucia Campus |
|
School of Biomedical Sciences
The University of Queensland,
BNE, QUEENSLAND 4072 |
|
| Telephone | +61 3365 2991 |
| Facsimile | +61 7 3365 1299 |
| s.millard@uq.edu.au |
Biography
I received a BA in Biology from Columbia University in New York City. After taking two years off to work as a research assistant, I began graduate school at Weill Cornell Graduate School of Medical Sciences, also in New York. My graduate advisor was Andrew Koff at the Sloan-Kettering Cancer Institute. I studied the cdk inhibitor, p27, and discovered that it is regulated at the level of translation as cells exit the cell cycle. I received my PhD in Molecular Biology in 2001.
My postdoctoral work was carried out in Larry Zipursky's lab at UCLA. Here, I learned both Drosophila genetics and neurobiology and began working on the Dscam-family of cell recognition molecules. I identified Dscam2 as the first tiling receptor and discovered that Dscam2 and Dscam1 are redundantly required for photoreceptor synaptic specificity.
I moved to Brisbane and began as a lecturer at the UQ School of Biomedical Sciences, in December 2009. I also have an Adjunct Appointment at the Queensland Brain Institute.
My postdoctoral work was carried out in Larry Zipursky's lab at UCLA. Here, I learned both Drosophila genetics and neurobiology and began working on the Dscam-family of cell recognition molecules. I identified Dscam2 as the first tiling receptor and discovered that Dscam2 and Dscam1 are redundantly required for photoreceptor synaptic specificity.
I moved to Brisbane and began as a lecturer at the UQ School of Biomedical Sciences, in December 2009. I also have an Adjunct Appointment at the Queensland Brain Institute.
Research Interests
Molecular mechanisms for wiring the brain
My lab is investigating the molecular mechanisms for wiring the brain using Drosophila melanogaster as a model system.
Dscam2 mechanistic studies
Dscam2 is a cell surface protein expressed on neurons and required for many different aspects of neurodevelopment. In the fly visual system, Dscam2 is a tiling receptor for lamina neuron L1 axons. Through a homophilic repulsive mechanism, this immunoglobulin domain-containing protein ensures that L1 axons target only within their column of origin. At a later stage of development, Dscam2 is required for synaptic specificity. Dscam2 and its closely related family member, Dscam1, ensure that photoreceptor synapses contain a specific composition of postsynaptic elements. This is accomplished through a self-avoidance mechanism; dendrites from the same neuron repel each other in a Dscam1 and Dscam2-dependent manner. How Dscam2 functions as a repulsive receptor in many different neurons is a major focus of the lab. I am particularly interested in whether neuron-specific alternative splicing of Dscam2 allows it to function broadly in the brain and a molecular-genetic system is currently being set up to address this issue. The lab is also investigating how Dscam2 mediates repulsion and to this end biochemical studies on the Dscam2 receptor-complex will be performed to identify co-receptors and/or signaling molecules required for repulsion.
Dscam2 mechanistic studies
Dscam2 is a cell surface protein expressed on neurons and required for many different aspects of neurodevelopment. In the fly visual system, Dscam2 is a tiling receptor for lamina neuron L1 axons. Through a homophilic repulsive mechanism, this immunoglobulin domain-containing protein ensures that L1 axons target only within their column of origin. At a later stage of development, Dscam2 is required for synaptic specificity. Dscam2 and its closely related family member, Dscam1, ensure that photoreceptor synapses contain a specific composition of postsynaptic elements. This is accomplished through a self-avoidance mechanism; dendrites from the same neuron repel each other in a Dscam1 and Dscam2-dependent manner. How Dscam2 functions as a repulsive receptor in many different neurons is a major focus of the lab. I am particularly interested in whether neuron-specific alternative splicing of Dscam2 allows it to function broadly in the brain and a molecular-genetic system is currently being set up to address this issue. The lab is also investigating how Dscam2 mediates repulsion and to this end biochemical studies on the Dscam2 receptor-complex will be performed to identify co-receptors and/or signaling molecules required for repulsion.
Dscam2 behavioural studies
The Dscam2 mutant has specific synaptic defects in the visual system. I am interested in how these changes in synaptic specificity affect the behavioural output of the fly. In collaboration with Bruno van Swinderen at QBI, we are using different visual system assays to determine whether Dscam2 mutants have behavioural phenotypes. The ultimate goal of this project is to link the wiring defects of the Dscam2 mutant brain to changes in visual system behaviour, and thereby gain a better understanding of why neural circuitry is connected in this way.
Complement, Neurodevelopment, and Disease
My lab is also investigating the role of complement in neurodevelopment and disease using sophisticated molecular genetics in the fruit fly. This project is collaborative effort between Trent Woodruff (NHMRC Career Development Fellow and Senior Lecturer), A/Prof. Pete Noakes, Prof. Steve Taylor (all at SBMS), and myself. Complement proteins are part of the innate immune system and play an important role in clearing pathogens and debris from the body. However, they have also been implicated in nervous system development and are commonly upregulated and/or activated in diseased brain tissue. We are taking two approaches to study this problem in the fly. First, we are investigating whether fly complement proteins are expressed in the brain during development and if so, whether they contribute to neural circuit formation. Second, we are manipulating complement genes in a fly model for Parkinson's Disease to determine whether these proteins abrogate or ameliorate hallmarks of the disease. In the long-term, we hope to apply what we learn in the fly to more complicated mouse and rat model systems.
Selected Publications
Millard SS, Lu Z, Zipursky SL, Meinertzhagen IA. (2010)Drosophila Dscam proteins regulate postsynaptic specificity at multiple-contact synapses. Neuron 9;67(5):761-8.
Millard SS, Zipursky SL. (2008) Dscam-mediated Repulsion Controls Tiling and Self-avoidance. Current Opinion in Neurobiology 18(1):84-9.
Hattori D, Millard SS, Wojtowicz W, Zipursky SL. (2008) Dscam-mediated Cell Recognition Regulates Neural Circuit Formation. Annual Reviews in Cell and Developmental Biology24:597-620.
Millard SS, Flanagan JJ, Pappu KS, Wu W, Zipursky SL. (2007) Dscam2 mediates axonal tiling in the Drosophila visual system. Nature 447(7145):720-4.
Wojtowicz WM, Flanagan JJ, Millard SS, Zipursky SL, Clemens JC. (2004) Alternative splicing of Drosophila Dscam generates axon guidance receptors that exhibit isoform-specific homophilic binding. Cell 118(5):619-33.
Available Hons and Postgraduate Projects
Investigating neuron-specific alternative splicing as a mechanism for restricting Dscam2 repulsion to individual cells.
How does Dscam2 signal repulsion?
The role of complement-like proteins in fly neurodevelopment. *
Manipulating Complement Proteins in a Fly Model for Parkinson's Disease. *
Correlating synaptic defects in the Dscam2 mutant with visual system behaviour. **
*collaboration with Dr Trent Woodruff, Associate Professor Pete Noakes, and Professor Steve Taylor (all SBMS)
** collaboration with Associate Professor Bruno van Swinderen (QBI)
On this site
- Home
- Academic Staff
- Dr Sean Millard
