#ScienceSaturday posts share exciting scientific developments and educational resources with the KAND community. Each week, Dr. Dominique Lessard and Dr. Dylan Verden of KIF1A.ORG summarize newly published KIF1A-related research and highlight progress in rare disease research and therapeutic development.
Direct observation of motor protein stepping in living cells using MINFLUX
To assess how somebody walks, the best method is to watch them walk. There is a lot of information that can’t be captured when a person is standing still: Their speed, posture, and the length of their stride are all useful metrics.
The same is true for motor proteins like KIF1A, but taking those measurements gets much more difficult at molecular scales. Like TVs and computer monitors, microscopes are under continuous development to improve their image quality:
- Spatial resolution: Like the sharpness of an image, this determines how clearly we can make out fine details, like the length of KIF1A’s step.
- Temporal Resolution: Like the framerate of a video, this determines how precisely you can see millimoment-to-millimoment changes. Too choppy and you can miss out on crucial changes, only seeing every other step of KIF1A.
In this week’s article, researchers collected high resolution recordings of the kinesin-1 motor protein as it walked along the microtubule. To do so, they tagged a single head of kinesin with a fluorophore, a small molecule that lights up when excited by (i.e. hit by) the lasers in microscopes. By tracking the fluorophore from multiple angles, the microscope was able to stitch together a more precise recording and catch subtle details about the movement of kinesin-1 in both preserved and live cells. They were able to determine the motor’s stride length, track them through crowded microtubule networks, and watch as they hopped from one microtubule to another. The technique was even able to track inactive kinesins that had fallen off the microtubule or were being dragged by other motors.
This high-resolution tracking could also be applied to other kinesins including KIF1A. Observing differences between KIF1A mutations that cause different symptoms could be particularly informative. It could also be used to evaluate the response of mutant KIF1A to direct therapeutics.
Novel Genetic Screening Tool Offers Hope for Babies Born With Life-Threatening Metabolic Disorder
Newborn genetic screening is a commonly advocated method of catching, and managing, genetic disorders early in life. But we all carry mutations in our DNA, most of which have no impact on our health. Determining whether a mutation in a gene is disease-associated is a complicated process that depends on prior literature and knowledge of protein structure. But this takes precious time for newborns with diseases like ornithine transcarbamylase (OTC) deficiency, which causes fatal ammonia buildup in the bloodstream and can occur rapidly after birth.
To speed up the screening process, researchers tested 1,500 different mutations in the gene causing OTC deficiency in yeast cells. By observing which yeast accumulated ammonia, the researchers were able to predict which mutations are more likely to cause OTC deficiency. Yeast can be genetically modified, grown, and tested quickly, and this screening could allow physicians to get the right resources to newborns with OTC deficiency faster.