The overall goal of the Millard lab is to understand how specificity is generated in the brain. This problem is best exemplified by considering that 100 trillion synapses are generated and maintained in the human brain using a toolkit of only 20,000 genes. We have been approaching this problem using molecular genetics in the fruit fly, Drosophila melanogaster. Most projects in the lab revolve around how a broadly expressed cell surface protein, called Down syndrome cell adhesion molecule 2 (Dscam2), is able to perform specific functions in different neurons. We are also interested in mechanisms of neurological disease, particularly those that involve changes in synaptic function.

Clones of mushroom body neurons in the Drosophila central brain generated using mosaic analysis with a repressible cell marker (MARCM).
Clones of mushroom body neurons in the Drosophila central brain generated using mosaic analysis with a repressible cell marker (MARCM).

 

We are always interested in recruiting enthusiastic scientists and welcome new ideas and techniques. Please contact Sean to enquire about Honours, Masters, PhD or Postdoctoral positions in the lab. Below is a list of ongoing projects.

Group Head

Staff

Students

For a full list of publications, visit eSpace

​2019

Li, JS and Millard SS (2019). Deterministic splicing of Dscam2 is regulated by Muscleblind. Sci Adv 5(1): eaav1678.

2018

Millard SS, Pecot MY (2018). Strategies for assembling columns and layers in the Drosophila visual system. Neural Development 13(1):11.

Kerwin SK, Li JS, Noakes PG, Shin GJ, Millard SS (2018). Regulated alternative splicing of Drosophila Dscam2 is necessary for attaining the appropriate number of photoreceptor synapses. Genetics 208 (2): 717-28.

2017

Lim NR, Shohayeb B, Zaytseva O, Mitchell N, Millard SS, Ng DCH, and Quinn LM (2017). Glial-specific functions of microcephaly protein WDR62 and interaction with the mitotic kinase AURKA are essential for Drosophila brain growth. Stem Cell Reports 9: 1-10.

2016

Tadros W, Xu S, Akin O, Yi CH, Shin GJ, Millard SS and Zipursky SL (2016). Dscam proteins direct dendritic targeting through adhesion. Neuron 89 (3):480-93.

2015

Li JS, Shin GJ, Millard SS (2015). Neuronal cell-type-specific alternative splicing: A mechanism for specifying connections in the brain? Neurogenesis 2:1, e1122699: 1-5.

Bosch DS, van Swinderen B and Millard SS (2015). Dscam2 affects visual perception in Drosophila melanogaster. Front. Behav. Neurosci. 9:149. doi: 10.3389/fnbeh.2015.00149.

2014

Lah GJ, Li JS, Millard SS (2014).  Cell-specific alternative splicing of Drosophila Dscam2 is crucial for proper neuronal wiring.  Neuron 17;83(6):1376-88.

2013

Li Q, Ha TS, Okuwa S, Wang Y, Wang Q Millard SS, Smith DP and Volkan-Cayirlioglu P (2013). Combinatorial rules of precursor specification underlying olfactory neuron diversity. Current Biol. 23, 2481-2490.

Paulk A, Millard SS, van Swinderen B.  (2013).  Vision in Drosophila:  Seeing the World Through a Model's Eyes.  Ann. Rev. Entomol. 58:313-32. 

2010

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.

2008

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 Biology 24:597-620.

2007

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.

Former lab members

  • Grace Shin (former postdoc) – currently doing a second postdoc at Columbia University
  • Danny Bosch (former PhD student, whereabouts unknown)
  • Kevin Mutemi (former MSc student) - enrolled in the EMBL PhD program, Germany
  • Josh Li (former PhD student) - postdoc Harvard Medical School

Our team

Sean Millard
Sean enjoys mountain biking and fishing in his free time.
Millard Lab team
The lab at the annual Australian Fly Meeting in Warburton, VIC
Nissa
Nissa is a caffeine-addict who is always looking for new places to drink a tasty brew. If you can’t find her at a coffee shop, she’ll be on a hiking trail somewhere in southeast Queensland or zipping around one of Brisbane’s many bike paths.
Kevin at Easter
Kevin’s drive to discover the unknown extends to Easter egg hunts...

Projects in the lab
We use Drosophila molecular genetics to understand:

  • how brain wiring proteins work at the molecular level.
  • how brain structures and neural circuits form.
  • how the brain generates sufficient protein diversity to specify its numerous synaptic connections - focus on alternative splicing.
  • how cell surface proteins regulate synaptic physiology.

We also use flies to model human disease processes. ALS is our current focus.

  • Modelling neurodegeneration in the fly eye using candidate ALS risk factors.
  • Studying how ALS risk factors affect motor neuron morphology, synaptic makeup and physiology.

 

Lab work flow and techniques
We use molecular biology to manipulate genes or the genome, perform genetics to generate animals of the appropriate genotype and then score the resulting phenotypes using confocal microscopy, electrophysiology or external phenotypes in the fly.

  • CRISPR
  • RNAi
  • Cell-specific overexpression
  • Mosaic experiments (single cells, rather than the entire organism, manipulated)
  • High resolution imaging
  • High-throughput screening in a whole animal model

Find out more about our research environment and how to apply to do a short or long-term research project with us.