Emmanuel Ngwoke Illuminates Mechanisms of Huntington's at Camp Sprague

Mark Walport states, “Science is not finished until it is communicated.” It is not enough to identify a problem and research the solution for the identified problem; researchers are expected to raise the next generation of scientists and bridge the wide gap in scientific knowledge between scientists and non-scientists through public engagements. To contribute towards the goal of bringing science to a non-technical audience, I had the opportunity to volunteer at the Camp Sprague social event held at Salt Lake City Public Library, Sprague Branch, in early fall. This event drew participants from all ages. I was very excited to share my science using relatable materials to illustrate the various biological processes I explore in my research.

I study the biology of Huntington’s Disease (HD) and intracellular trafficking at the School of Biological Sciences, University of Utah. HD is an inherited incurable disease that can be passed down from affected individuals to their children. HD leads to the death of brain cells known as neurons. The loss of these neurons makes affected individuals not perform optimally by experiencing memory loss, poor motor skills, and, ultimately, death. What causes the disease? How is HD killing brain cells?

HD is caused when an irreversible change in the huntingtin gene happens. This irreversible change is known as mutation, and it can happen randomly. The mutated huntingtin gene makes a bad huntingtin protein known as mutant huntingtin. The mutant huntingtin protein has a long stretch of glutamine (Q) amino acid repeats and other amino acids. Twenty (20) known amino acids can form the building block of proteins. One amino acid is not better than the other. However, in the case of the huntingtin protein, having more than 35 glutamine amino acid repeats makes the protein unfit to perform its regular biological role. What happens is that the mutant huntingtin protein cannot fold correctly in a way that the cell can handle, forming aggregates. The huntingtin aggregate formation burdens brain cells, leading to their death. Since gene changes, including the huntingtin gene, are not reversible, my strategy is to explore how cells can eliminate the lousy huntingtin aggregates. This approach involves moving the cellular garbage truck, referred to as lysosomes, around the cell to where the mutant huntingtin proteins are for destruction.

The goal for my public engagement during Camp Sprague at SLC Public Library, Sprague Branch, is to bring awareness to HD and share the thinking behind my research approach. My engagement activities involved three main objectives – showing the difference between the bad mutant huntingtin and the good one, description of huntingtin aggregation, and demonstrating the degradation of mutant huntingtin by lysosomes. Before I began my engagement activity, I asked participants if they knew what HD is. Surprisingly, the majority did not know what it was. I used the opportunity to educate them on what HD is.

To demonstrate the difference between the regular and mutant huntingtin proteins, I gave each participant a set of paper links of different colors. Paper links of a particular color would represent the glutamine amino acid, while other colors would represent other amino acids. To make the regular huntingtin protein, participants were asked to string 25 paper links of a particular color together to represent the polyglutamine repeats. Next, I told participants to flank the strung polyglutamine repeats with different colors of paper clips and label it the “good huntingtin protein”. As for making the mutant huntingtin protein, I asked participants to string paper clips of a particular color containing 40 paper clip units to represent longer polyglutamine repeats. This would be labeled as the “bad huntingtin protein .” I asked participants to compare the lengths of the strings and share what they think about these two proteins.

To describe misfolded protein and protein aggregation, I provided sheets of paper and envelopes for the participants. I demonstrated a simple folding guide representing proper protein folding in the cell for participants to imitate. Each participant was told to fold the paper sheets provided according to my demonstration and labeled “properly folded protein”. To demonstrate protein misfolding, I told participants to randomly crumple the paper sheets and label them “misfolded protein .” Next, I asked the participants to put each “protein” in the provided envelope and share their experiences. They reported that placing the properly folded sheet into the envelope was easier than when the sheet was crumpled – that is, “misfolded.” With this demonstration, the participants felt that protein misfolding could burden brain cells, leading to their death.

Finally, I first described lysosomes as garbage trucks to demonstrate the lysosomal degradation of misfolded protein. Like garbage trucks that move around in the street collecting trash for recycling or destruction from house to house, lysosomes can also move around in the cells, fusing with materials cells want to get rid of. Lysosomes have hydrolytic enzymes in them, which make them destroy any materials cells do not want. I asked participants to make a cell using different playdough colors to represent various cell components for this engagement activity. This cell will have a nucleus and lysosomes (the garbage truck) spread across the cell, representing a healthy cell. Next, I asked participants to make the healthy cells sick by adding a large blob of playdough next to the nucleus to represent the mutant huntingtin protein aggregate. This time, participants were told to relocate the dispersed lysosomes (the garbage truck) to where the mutant huntingtin aggregate is while reducing the large blob of the mutant huntingtin protein to a speck to indicate its degradation by lysosomes.

At the end of my engagement activity, participants learned about HD and the role some cell components can play in slowing down HD progression in affected individuals. I also showed them microscopy images I took from my lab of what live cells with or without huntingtin aggregates look like in real life, which increased their curiosity. In my reflection, I am reminded of how much people do not know about how we think science and why science should be for everybody.

I want to thank Amber and Taylor – the staff of SLC Public Library, Sprague Branch, for their incredible support during the planning of my engagement activity. I had a good experience working with the library and look forward to future engagement opportunities with them.