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Molecular motors are the engines of the cell, converting chemical energy into mechanical forces that power the movements essential for life.
Our research focuses on an outstanding question in the field: how do cells harness and regulate motor activity to support a wide range of biological functions?
We study this problem in the context of neurosensory cells, which have highly specialized morphologies optimized for sensory transduction. We investigate how motor proteins shape these distinctive cellular architectures and also how they mediate the sensory functions of these cells.
Ongoing Projects:
Myosin-7a in auditory function and disease
Auditory hair cells convert sound stimuli into neural signals. They achieve this through mechanotransduction, which occurs at the tips of specialized cellular protrusions called stereocilia. The motor protein myosin-7a is essential in the development and function of these stereocilia. Mutations in the myosin-7a gene (USH1B) are the leading genetic cause of Usher syndrome, the most common form of deaf-blindness in humans.
The goal of our research is to understand how myosin-7a activity is regulated in stereociliary protein trafficking and mechanotransduction and to uncover the mechanisms behind Usher protein-related vision and hearing loss.
Kinesin-2 in ciliary trafficking and retinal ciliopathies
Cilia are microtubule-based cellular protrusions essential for sensing the external environment. In the retina, the outer segment (OS) of the photoreceptor cells is a specialized light-sensitive cilium responsible for transducing light into neural signals. Genetic defects in cilia cause a group of inherited conditions, known as ciliopathies, with clinical manifestations often including retinal dystrophy and blindness.
The assembly and function of cilia requires a sophisticated protein trafficking system, known as the intraflagellar transport (IFT) train. Kinesin-2 motors power the movement of this train to the tips of the cilia. Mutations in kinesin-2 are therefore linked to various types of ciliopathies including retinitis pigmentosa.
Our research aims to uncover the molecular mechanism by which kinesin-2 powers the transport of the IFT train along cilia, how this is regulated, and how mutations disrupt this process, leading to ciliopathies and vision loss.
Kinesin-2 motors in neuronal transport
In additional to its role in ciliary transport, kinesin-2 also plays a role in transport within neurons. The requirements for transport in cilia and neurons are quite different due to the size differences between the two.
We are investigating the mechanisms by which kinesin-2 is able to switch between transport in these two systems and the specializations it has acquired for functioning in each mode of transport.
Our Approach
We employ a multidisciplinary approach that combines biophysics, biochemistry, and cell biology. We integrate high-resolution live-cell imaging with advanced single-molecule techniques to directly visualize motor protein dynamics both in vitro and in vivo. The bottom-up approach of building complex systems from their basic components provides a powerful system for understanding how motor proteins function. When coupled with a top-down approach of manipulating motor proteins in cells, this has enabled us to uncover novel mechanisms of myosins and kinesins across diverse biological processes, guiding our efforts to identify new therapeutic targets for motor-related human diseases such as deafness and blindness.
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