Research Projects
The Role of Kinesin in Experience-Dependent Dendritic Spine Plasticity in Neurodevelopment


Programme(s) to which this project applies:

☒ MPhil/PhD ☑ MRes[Med] ☒ URIS
About the Project

Objective and Significance:

Experience-dependent synapse-specific modifications have been proposed to be crucial for synaptic pruning during the critical periods of neurodevelopment. Because both transcription and translation are required for synaptic modifications, dendritic transport via motor proteins delivering targeted gene products from the nucleus to the vast dendritic tree becomes extremely crucial for the synaptic pruning process. Dendritic spines are highly dynamic and plastic during neurodevelopment. In neurodevelopmental diseases such as autism spectrum disorders (ASD), impairments in dendritic spine plasticity with increased filopodia-to-spine ratios and abnormal protrusion densities have been observed in both patients and animal models during critical periods. These dendritic spine pathologies are thought to be caused by pruning deficits during the critical period of neurodevelopment. Kinesin 1 is a motor protein that plays important roles not only in axonal transport but also dendritic transport. Several kinesin 1 cargos, such as fragile X mental retardation protein, AMPA receptor GluR2 subunit, and mitochondria, have been shown to play key roles in synaptic plasticity. These findings led us to hypothesize that KIF5B, a gene that encodes motor protein kinesin 1, plays a crucial role in specific experience-dependent dendritic spine plasticity and synaptic pruning in neurodevelopment.

Research Plan and Methodology:

We will use KIF5B conditional knockout mice to study dendritic spine plasticity during neurodevelopment in vivo using two-photon transcranial imaging during the critical periods and in adulthood. We will also test the behaviour of KIF5B conditional knockout mice to determine if they exhibit features characteristic of autistic animal behaviour. Next, we will evaluate the role of KIF5B in the experience-dependent pruning of dendritic spines in the barrel cortex by sensory deprivation and in an enriched environment. Last, we will label both excitatory and inhibitory synapses in KIF5B conditional knockout mice by in utero electroporation to examine the synaptic plasticity during the critical periods to reveal the role of KIF5B in excitatory and inhibitory synapse stability and in dendritic spine plasticity. Taken together, our findings will reveal the fundamental and novel roles of KIF5B in synapse maintenance, dendritic spine plasticity, and experience-dependent pruning in neurodevelopment. We can also explore the possible use of KIF5B conditional knockout mouse model for studying ASD.

About the Supervisor

Dr CSW Lai, School of Biomedical Sciences

Biography
coraswl@hku.hk

Next Step?

For more information or to express interest for this project, please email the supervisor or the specified contact point in the project description.  Interested candidates are advised to enclose with your email:

  1. your CV,
  2. a brief description of your research interest and experience, and
  3. two reference letters (not required for HKUMed UG students seeking MRes[Med]/URIS projects).

Information on the research programme, funding support and admission documentations could be referenced online at the Research Postgraduate Admissions website. General admission enquiries should be directed to rpgmed@hku.hk.

HKUMed MBBS students interested in the Master of Research in Medicine (MRes[Med]) programme may visit the programme website for more information.  

HKUMed UG students interested in the Undergraduate Research Internship Scheme (URIS) may visit the scheme’s website for more information.