Eureka!

60 Seconds with Shermali Gunawardena

There is a complex highway system inside our minds. In each brain cell, thread-like roadways called microtubule tracks ferry proteins and other precious cargo from place to place. This highway system facilitates normal cell function. But what happens when traffic jams occur? Alzheimer’s disease may be one answer, says UB biologist Shermali Gunawardena.

Nanoparticles—which may one day carry drugs to blockages—glow red along the axons of fruit fly neurons. Photo: Shermali Gunawardena and Plos One

Shermali Gunawardena, Research Assistant Professor, Institute for Lasers, Photonics and Biophotonics

What do the highways in our brains look like?
The cells in our brain are called neurons, and each one has a long, cable-like projection called an axon. This is where the microtubule tracks are. When everything is functioning normally, proteins called motor proteins—which you can analogize to tiny trucks—move in two directions along the tracks, transporting materials from one end of the cell to the other.

What materials travel along the microtubule roadways?
The cargo can include protein complexes, which are sometimes arranged inside a bubble called a vesicle. There are also cellular structures, such as mitochondria, which are like tiny power plants.

Why is it so critical that traffic flow smoothly?
A functioning transport system is required for viability, that is, for cells to grow and sustain themselves. Without these pathways, cells die because components they need become unavailable.

You study the blockages, or traffic jams. Why?
Transport problems may be an early event in the development of degenerative diseases, like Alzheimer’s. Blockages seem to occur well before problems like senile plaques and cell death are observed.

Can you actually see the blockages?
Yes. We have seen them using microscopy. When there is a defect, you have these huge blocks of accumulated vesicles or organelles.

What are some of your specific research findings?
We are slowly building on the foundation of how motor proteins move and how problems in motor movements can lead to blockages. In one study, we found that a protein called presenilin helps keep motors moving properly. If you take it away, problems occur. Mutations in presenilin have long been linked to Alzheimer’s disease, and our work shows one possible reason for this.

Where do you see this research leading in terms of future treatments?
If a traffic blockage can cause a lot of negative downstream effects, then the easiest way to solve the problems that blockage is causing is to make traffic move more smoothly. One thing we are exploring is how to use nanoparticles to cage drugs and release them at the blockage.