Dr Zhitao Hu

Contact Information

Building: QBI Building #79
Room: 431
Tel: +61 7 334 66395

Mailing Address

Queensland Brain Institute
The University of Queensland
Brisbane, 4072

Short biography

Research directions

Current collaborations

Selected publications

PhD and Honours projects


Short biography

Dr. Zhitao Hu received his PhD in 2008 from Huazhong University of Science and Technology in China. Under the supervision of Professor Tao Xu, his study was focusing on calcium dependent Dense Core Vesicle (DCVs) release in different cell type. In the last two years of his PhD, he switched to C. elegans to study the behavior plasticity (learning and memory) and neural circuit function. In 2008, Dr. Hu joined professor Josh Kaplan’s lab to begin his postdoctoral career at Massachusetts General Hospital and Harvard Medical School, USA. He continued to use C. elegans as the genetic model to investigate the molecular and cellular mechanism of neurotransmission. In May 2015, Dr. Hu was appointed as a Group Leader to establish his independent research laboratory at the Clem Jones Centre for Ageing Dementia Research in Queensland Brain Institute, the University of Queensland.

Research directions

Over the last few decades, one of most important objectives in the field of neuroscience has been to understand the molecular and cellular mechanisms that regulate neurotransmitter release, which drives neuronal communication in the nervous system. Many model organisms have been used to address this question, including the mouse, fly, zebrafish, nematodes and octopus. Among these organisms, C. elegans has emerged as a powerful genetic model to study the synaptic function. In the past 20 years, numerous studies in C. elegans have significantly promoted the development of this field, with the development of sophisticated electrophysiology and imaging techniques in this organism. Combining the electrophysiological recording, cellular imaging, molecular biology, and biochemistry approaches, we are currently focusing on four lines of research:

1. Kinetics regulation of synaptic vesicle release

Neurotransmitter release is tightly regulated and thought to occur in a number of steps, in which the vesicles are tethered to the release site, primed and fused with the plasma membrane. The final fusion is quite fast (occurs in milliseconds) in response to calcium influx. During this process, the vesicles can be released at different kinetics, termed as fast and slow release. Over the past few decades, a large number of synaptic proteins affecting the amount of synaptic release have been identified. However, the effects of the experimental manipulation on the release kinetics have not been largely investigated. Understanding of how release kinetics is determined has broad implications. The speed of the neurotransmission limits the efficiency and the communication rate between neurons and strongly influences local circuit dynamics. The release kinetics has profound effects on the circuit development and cognition, as well. We are focusing on synaptic proteins which affect release kinetics to determine the underlying molecular mechanism.

2. Molecular/Cellular mechanism of different release forms

Neurotransmitters can be released in two forms: evoked fusion after an action potential, and spontaneous fusion (termed “minis” or mEPSC). Increasing evidences show that the spontaneous and evoke do not always change at the same trend, indicating that different fusion machinery for these two release forms. Although the physiological function is still uncertain, spontaneous release has been proposed to be important in multiple processes: including long-term facilitation induction, homeostatic synaptic plasticity modulation, postsynaptic receptors clustering at the release site, etc. There is evidence that vesicles driving these two modes of release are supplied by different pools. For example, studies have demonstrated that a large portion of spontaneously released vesicles are drawn from a pool other than the readily releasable pool that normally gives rise to evoked release. Despite these efforts on spontaneous and evoke release, the molecular mechanism however, remains unclear. We will focus on those mutants in which the two kind of release are differently regulated and determine the cellular mechanism.

3. Synaptic transmission defect of neurological diseases

Recent advances in genomic and bioinformatics technologies have identified DNA variants that are associated with neurological disorders like Autism and motor neuron disease. Demonstrating a functional role for the genes linked to the disorders is the first step in prioritising follow-up studies. As a widely used tool in neuroscience, C. elegans provides a cost-effective strategy to validate the genes identified in human genetic studies by studying their functional role in neurotransmission. We will focus on those candidate genes and dissect their functional importance in synapses.

Current collaborations

  • Professor Josh Kaplan - Harvard University, Boston, USA

  • Professor Tao Xu – Chinese Academy of Sciences, Institute of Biophysics, Beijing, China

  • Associate Professor Jeremy Dittman - Cornell University, New York, USA

  • Assistant Professor Kavita Babu - Indian Institute of Science Education & Research (IISER), Mohali

  • Professor Zhiqi Xiong - Institute of Neuroscience, Chinese Academy of Sciences, Shanghai, China

Selected publications 

Seungwon Choi, Kelsey P. Taylor, Marios Chatzigeorgious, Zhitao Hu, William R. Schafer, Joshua M. Kaplan. Sensory Neurons Arouse C. elegans Locomotion via Both Glutamate and Neuropeptide Release. PLoS Genetics. 2015. Jul 8; DOI: 10.1371/journal.pgen.1005359

Zhitao Hu, Amy B. Vashlishan-Murray and Joshua M. Kaplan. NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release. Journal of Neuroscience,

Zhitao Hu, Xia-Jing Tong and Joshua M. Kaplan. UNC-13L, UNC-13S, and Tomosyn form protein code for fast and slow neurotransmitter release. Elife, 2013 August 13.

Sun Y, Hu Z, Goeb Y, Dreier L. The F-Box Protein MEC-15 (FBXW9) Promotes Synaptic Transmission in GABAergic Motor Neurons in C. elegans. PLoS One. 2013;8(3):e59132.

Zhitao Hu, Sabrina Hom, Tambudzai Kudze, Xia-Jing Tong, Seungwon Choi, Gayane Aramuni, Weiqi Zhang, Joshua M. Kaplan. Neurexin and Neuroligin Mediate Retrograde Synaptic Inhibition in C. elegans. 2012, Science 337 (6097): 980-984

Jason P Chan, Zhitao Hu, and Derek S Sieburth. Recruitment of sphingosine kinase to presynaptic terminals by a conserved muscarinic signaling pathway promotes neurotransmitter release. 2012. GENES & EVELOPMENT 188003(US 21557)

Yingsong Hao, Zhitao Hu, Sieburth, D.and Joshua M. Kaplan.(2011) RIC-7 Promotes Neuropeptide Secretion. PLoS Genetics. 2012. Jan 19; 8(1):e1002464

Katherine Thompson-Peer, Jihong Bai, Zhitao Hu, and Joshua Kaplan. HBL-1 patterns synaptic remodeling in C. elegans. (2011). Neuron. 2012. Feb 9, 73:453-465

Zhitao Hu, Edward C.G. Pym, Kavita Babu, Amy B. Vashlishan Murray and Joshua M. Kaplan.(2011) A neuropeptide-mediated stretch response links muscle contraction to changes In neurotransmitter release. Neuron. 2011. Jul 14;71(1):103-16

Kavita Babu, Zhitao Hu, Shih-Chieh Chien, Gian Garriga, and Joshua Kaplan. (2011). The Immunoglobulin super family protein RIG-3 prevents synaptic potentiation and inhibits Wnt signaling. Neuron. 2011. Jul 14;71(1):92-102

Martin JA*, Hu Z*, Fenz KM, Fernandez J, Dittman JS.(2011). Complexin has opposite effects on two modes of synaptic vesicle fusion. Curr Biol. Jan 25;21(2):97 105 (*,co-first author)

Jihong Bai, Zhitao Hu, Jeremy S. Dittman, Edward C.G. Pym and Joshua M. Kaplan. (2010). Endophilin Functions as a Membrane-Bending Molecule and Is Delivered to Endocytic Zones By Exocytosis. Cell, Volume 143, Issue 3, 430-441

Hu,Z., Dun,X., Zhang,M., Zhu,H., Xie,L., Wu,Z., Chen,Z., and Xu,T. (2007). PA1b, a plant peptide, induces intracellular [Ca2+] increase via Ca2+ influx through the L type Ca2+ channel and triggers secretion in pancreatic beta cells. Sci. China C. Life Sci. 50, 285-291

Hu,Z.T., Zhao,P., Liu,J., Wu,Z.X., and Xu,T. (2006). Alpha-latrotoxin triggers extracellular Ca2+ dependent exocytosis and sensitizes fusion machinery in endocrine cells. Acta Biochim. Biophys. Sin. (Shanghai) 38, 8-14

Hu, Z.T., Chen, M.R., Zhao, P., Dong, Y.M., Zhang, R.Y., Xu, T. and Wu, Z.X. (2008).Synaptotagmin IV regulates Dense Core Vesicle (DCV) release in LβT2 cells. Biochem Biophys Res Commun, 371 781-786

Liu,H.S.*, Hu,Z.T.*, Zhou,K.M.*, Jiu,Y.M., Yang,H., Wu,Z.X., and Xu,T. (2006). Heterogeneity of the Ca2+ sensitivity of secretion in a pituitary gonadotrope cell line and its modulation by protein kinase C and Ca2+. J. Cell Physiol 207, 668-674 (*,co-first authors)

Yang H, Liu H, Hu Z, Zhu H, Xu T. (2005). PKC-induced sensitization of Ca2+ dependent exocytosis is     mediated by reducing the Ca2+ cooperativity in pituitary gonadotropes. J. Gen Physiol 125(3):327 34 18. Ge,Q., Dong,Y.M., Hu,Z.T., Wu,Z.X., and Xu,T. (2006). Characteristics of Ca2+exocytosis coupling in isolated mouse pancreatic beta cells. Acta Pharmacol. Sin. 27, 933-938.

JIU Yaming*, HU Zhitao*, LIU Jie*, WU Zhengxing, XU Tao. (2006) α-LTX and α-LTXN4C induce [Ca2+]i elevation through different mechanisms in pancreatic β cells. Chinese Science Bulletin, 51 (2) 158-163.

PhD and Honours projects

If you are highly motivated and interested in pursuing graduate studies (PhD and Honours), please contact Dr Hu (uqzhu4@uq.edu.au) for more information on available projects.