#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, Science Communication Associate Aileen Lam and Chief Science Officer Dr. Dominique Lessard. Send news suggestions to our team at impact@kif1a.org.

New Resource From KIF1A.ORG

There is no treatment for KIF1A-Associated Neurological Disorder. We’re here to change that. Hear from our Chief Science Officer, Dr. Dominique Lessard, in this community update on our therapeutic development strategy!

“We move very quickly while working against a timeline that has historically moved very slowly. Therapeutic development doesn’t move fast enough for the rare disease community. That’s an unfortunate fact. We could accept that fact, & move along at a pace that is too slow. But we’re not going to do that. Instead, we challenge this timeline and utilize tools and connections and resources that allow us to push the pace and reach our goals more quickly.”

KIF1A.ORG In The News

Kamloops Child Diagnosed With Rare Genetic Disorder

In this interview, Amanda Burritt, mom to KIF1A superhero Emma, shares their family’s KIF1A story, from the challenges of their diagnostic odyssey to how KIF1A/KAND impacts every aspect of their lives. Click the button below to listen.

Recent KIF1A-Related Research

Reconstitution of Kinesin-1 Activation

The world of kinesins continues to contain mysteries for further exploration. Importantly, research regarding these topics is ongoing to gain a better understanding of how these magnificent motor proteins function and are regulated. For this week, we will be talking about kinesin-1 (KIF5), a relative of kinesin-3 (KIF1), and how it is activated to carry out cargo transport. With this insight into how kinesin activity is regulated, we can ask similar questions with KIF1A to determine if there are shared mechanisms between the two families regarding how cells control intracellular transport. 

Before diving into this paper, let’s go over some important terms and concepts that we may come across. As this paper focuses on activation, it is also good to note that kinesin has an inactivated, or an autoinhibited, state that prevents the excess usage of energy when the motor is not carrying cargo. Looking at structure, kinesin functions as a tetramer, a complex made of four different parts that consist of two kinesin light chains (KLCs) and two kinesin heavy chains (KHCs). In addition to other structures such as the C-terminal domain (at the end of the protein) and N-terminal motor domain (at the beginning of the protein), these distinct units that make up the kinesin motor protein play an integral role in regulating activation and autoinhibition. 

In this pre-print paper, researchers have proposed a model regarding the activation and autoinhibition of kinesin-1. They show that the KLC is involved in the autoinhibition process in a way that is independent from the kinesin inhibition attributed with the KHC. Additionally, their data gives evidence that both a microtubule-associated protein (MAP), MAP7, and a cargo adapter protein, nesprin-4, help activate kinesin activity by enhancing its transport and association on microtubules, respectively. Overall, this paper details a two-factor activation mechanism for kinesin-1 where nesprin-4 relieves an autoinhibitory block and MAP7 enhances kinesin transport activity. These results suggest that a coupled process of cargo-adapter mediated release of autoinhibition and MAP recruitment to microtubules is a supported model for kinesin activation, which provides us with more insight into how kinesin motors are regulated.

The collaborative work featured in this paper was conducted entirely by KIF1A.ORG Research Network members the McKenney Lab, Ori-McKenney Lab and Niwa Lab. We are so thankful to have this powerhouse team of researchers as a part of our mission! If you want more details on how these researchers came to this conclusion, check out the paper below.

Rare Disease News

RNA worked for COVID-19 vaccines. Could it be used to treat cancer and rare childhood diseases? 

2020 brought about some unprecedented times with the COVID-19 pandemic, but as of recently, the light at the end of this tunnel has presented itself in the form of a RNA-based vaccine! Not only is it helping to protect people from the coronavirus, but researchers are now thinking about how to use this RNA approach for cancers and rare diseases. In this article, the author explores this idea of using messenger RNA (mRNA) to genetically instruct cells in the body to produce specific proteins as a way to treat a variety of diseases. In particular, scientists are looking to use this technique to address diseases where patients are deficient in proteins that can be replenished with this RNA approach. Additionally, they are looking to target these diseases during pregnancy in order to prevent the progression of developmental delay, which is harder to treat after birth. 

Of course, this technique doesn’t come without its obstacles. In the early 2000s, scientists focused on and successfully created RNA that could be safely administered to the human body without causing inflammation. Currently, researchers are working to address RNA’s tendency to degrade quickly by using lipids, or fatty substances, as a delivery vehicle to transport it across our membranes and prevent it from breaking down. From these experiments, they found that different types of lipids targeted specific organs in the body, which has led them to focus on optimizing this delivery method so that scientists will have better control of where the RNA goes when administering these injections in the future. When it comes to using this approach for cancer, the idea is to create a therapeutic vaccine that makes the proteins found in a patient’s tumor as a way to alert the immune system to destroy the tumor itself. Since cancer cells are very good at escaping an immune reaction, the hope with the RNA therapeutic vaccine is that it will help overcome this suppressed immune response to cancers. All in all, this COVID-19 vaccine has the gears turning for many scientists, as a similar plan of attack could be applied to other illnesses, such as cancers and rare diseases. To read more about RNA vaccines and the therapeutic potential it brings, check out the article and video below!

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