#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 impact@kif1a.org.

Recent KIF1A-Related Research

Expansion of the phenotypic spectrum of de novo missense variants in kinesin family member 1A (KIF1A

HUGE news this week for our KAND community! This week we are featuring a newly published study from the Murdoch Children’s Research Institute in Melbourne, Australia. This publication is a collaborative scientific effort made possible in part by many KIF1A scientists in our Research Network. Broadly, this study investigates the overlap in phenotypic characteristics between KAND and Rhett syndrome resulting from KIF1A mutation. Throughout the manuscript, four specific KIF1A mutations (Cys92Arg, Thr99Met, Asp248Glu, Pro305Leu) are comprehensively characterized at a clinical level. While Thr99Met is one of the most widely reported KIF1A mutations in scientific literature and is already known to have impaired function, the remaining KIF1A mutations listed above have been comparatively understudied. As a result, Cys92Arg, Asp248Glu, and Pro305Leu were further characterized at the cellular and molecular level. Upon investigation, it was discovered that all three of these mutations have impaired motor function within cellular assays. On a molecular level however, the effect of each mutation became more clear. Specifically, we learn that while all three of these mutations impair KIF1A velocity (how fast it can move), Cys92Arg and Pro305Leu KIF1A mutations also have dramatically impaired binding to the microtubule roadway. From this study we gain a deeper understanding of how 1) certain KIF1A mutations impair motor function and 2) how this impairment in motor function can present at a clinical level in specific cases. It is important to note that this is the second research paper within the month of July that acknowledges KAND as a disorder caused by KIF1A mutations. Thank you to all involved with this publication to help paint a picture of KIF1A and KAND to the research world!

Rare Disease News

New Clues To ALS And Alzheimer’s Disease From Physics

What do a boiling pot of water and certain neurodegenerative brain disorders have in common? Phase transitions! A phase transition is defined as the point in which a substance transitions from one phase of matter (solid, liquid or gas) to another phase of matter, like when a pot of liquid water boils to form steam. While the concept of phase transitions in our cells has been around for a while, the study of cellular phase transition has entered a renaissance of investigation over the past 5-10 years. Specifically, there has been an increase in our attempt to understand how phase transitions in cells may be altered or cause cellular harm in certain neurodegenerative disorders such as Alzheimer’s disease and ALS. Take a look at this article that overviews the history of studying cellular phase transitions, how these phase transitions relate to neurodegenerative conditions, and how tackling phase transitions could be potential therapeutic target.

What Taylor found was gene mutations that caused abnormal phase transitions in cells. And he found evidence of similar mutations in other neurodegenerative diseases. This research earned Taylor the 2020 Potamkin Prize, a big deal in Alzheimer’s research. And it got a lot of biotech companies thinking about ways to fix problems with phase transitions inside cells.

Scientists achieve first complete assembly of human X chromosome

The Human Genome Project was one of the most impactful collaborative feats in recent scientific history. Taking almost 13 years, this project discovered the sequences of all of the genes in the human genome advancing the field of genetic and genomic discovery at warp speed. Despite this massive feat, there is still much to be learned about how all of these genes are arranged at a chromosomal level as no one chromosome has been genetically mapped and arranged, end-to-end, with no gaps. Until now. Researchers at the University of California Santa Cruz have succeeded in this landmark achievement by assembling the entire human X chromosome from end-to-end. To complete this task, researchers took on one of the most complex jigsaw puzzles of all time. In this process scientists would take massive amounts of DNA sequences, each representing a part of the X chromosome, and try to fit them all together. However, many of these DNA sequences overlapped and repeated, leading them to turn to high-power computational tools to resolve the full chromosome map. In tandem with this discovery, authors on this research paper have also co-founded the Telomere-to-Telomere consortium with the hope of mapping all human chromosomes from end-to-end.

‘Bystander’ Cs meet their match in gene-editing technique

While the basics of CRISPR technology first emerged in 1987, there have been many recent advancements focused on improving our CRISPR toolbox to help treat human disease. In recent Science Saturday posts, we have discussed new improvements in the DNA base-editing capabilities of CRISPR tools. As a reminder, DNA is made up of four base pairs: adenine (A), cytosine (C), guanine (G), and thymine (T). This article highlights a technological advancement from biomolecular engineers at Rice University aimed at editing the cytosine DNA base. Mutations involving cytosine base pairing account for ~38% of human pathogenic diseases, making this type of base editing an enticing candidate for optimization. Previous CRISPR technology often had a difficult time distinguishing between a “bad” cytosine (disease relevant) and a “good” cytosine (non-disease relevant). Findings from this study help tackle this problem by increasing the accuracy of cytosine editors by 6000-fold! Have a look at this article to learn more about this new version of CRISPR. Additionally, with all of our recent chatter about both DNA and RNA editing techniques, we encourage you to watch the video below to learn more about the structural differences of DNA and RNA and why both types of this genetic material are important in our bodies!

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