#ScienceSaturday posts share relevant and exciting scientific news with the KAND community. This project is a collaboration between KIF1A.ORG’s Research Engagement Team Leader Alejandro Doval, President Kathryn Atchley and Science Communication Director Dr. Dominique Lessard. Send news suggestions to our team at firstname.lastname@example.org.
What Inspires A Clinical Researcher?
This week we are sharing another CheckRare interview with Dr. Wendy Chung. Dr. Chung heads our main clinical team at Columbia University and is the leading clinical expert on KIF1A Associated Neurological Disorder. In this short video Dr. Chung shares what inspires her as a clinical researcher studying KIF1A/KAND. Dr. Chung, we are beyond thankful for your relentless dedication to our community!
Recent KIF1A-Related Research
Pathogenic Mutations in the Kinesin-3 Motor KIF1A Diminish Force Generation and Movement Through Allosteric Mechanisms
Today we are thrilled to present a new pre-print paper from two of our Research Network members, the Gennerich Lab and the Verhey Lab! We often say that kinesin motors act as a “molecular machine”… but what does this actually mean? By definition, a machine is “a mechanical structure that uses power to apply forces and control movement to perform an intended action.” KIF1A movement is discussed quite often in scientific literature as KIF1A has some very impressive movement capabilities in comparison to other kinesin motors. This study explored another important aspect of KIF1A function that has only briefly been touched upon in the literature: what about the force aspect of KIF1A function that helps it act as a machine in our cells? Findings from this study revealed new information about the pattern of force production as well as how “strong” KIF1A is on the microtubule track in comparison to other kinesin motors. Intriguingly, we now know that KIF1A is doing something very novel. While KIF1A is not as “strong” as other conventional kinesin motors, it does exhibit a unique pattern of force production. This means that while a KIF1A motor may detach from the microtubule track more easily than other motors, they can rapidly reattach leading to a characteristic “clustering” of force events.
Furthermore, this study characterizes two KAND-related variants that are located in important regions for force production: V8M and Y89D. It was found that both of these mutations dramatically impair KIF1A force production (“strength”) but do not impair KIF1A’s ability to reattach to the microtubule- fascinating! Introducing these mutations also reduced KIF1A’s velocity (how fast), run length (how far), and landing rate (how efficient at landing on the microtubule). Lastly, this study asked another important question related to our current hypothesis of heterozygous KAND mutations: what happens when a mutant KIF1A protein dimerized, or pairs up, with a non-mutated KIF1A? In this case, it was found that mutant KIF1A/non-mutated KIF1A parings dramatically impair motor function. Thank you to the Gennerich and Verhey labs for your work and for being active members in our Research Network. Click the button below to read this study!
Rare Disease News
Data robustness and reproducibility in gene editing applications: today’s limits and tomorrow’s potential
CRISPR, CRISPR, CRIPSR! It’s a word we hear a LOT in the therapeutic development space, particularly as it relates to the gene editing of rare monogenetic neurological disorders like KAND. So, what do researchers think about all of this CRISPR buzz? This article answers that question by interviewing a number of different researchers and highlighting their experiences and opinions about the future of this technology. Give it a read! Do you have some time on your hands and want to learn more about CRISPR? Have a listen to one of my (Dr. Dom’s) favorite podcast episodes on CRISPR from Radiolab. It’s informative, communicated at a lay-level, and quite entertaining!
Misfiring brain cells may cause swallowing woes in children with developmental disorders
For many KAND patients, muscle atrophy and control around the throat and tongue can lead to difficulty swallowing and risk of aspiration. This article, covering findings from neuroscientists at Virginia Tech and George Washington University, may help us understand why this is the case. It turns out that in a mouse model of DiGeorge syndrome (characterized in part by difficulties swallowing or eating) the motor neurons that control the tongue were misfiring. These neurons are responsible for the back and forth movement of the tongue that is needed to efficiently swallow. What can we learn from this? It makes sense that if these neurons are misfiring, or behaving improperly, that the muscular control needed to safely eat and swallow could be impaired. This also presents a potential therapeutic target by finding ways to calm and recalibrate the motor neurons of the tongue. As a friendly reminder, we’ve also included a video that explains some rescue techniques to help someone who is choking. Whether this is your first time learning these techniques or if this is a refresher for you, it never hurts to be prepared so that you are ready to act in a situation such as this.