Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) - 01.23.19

Overview | Description | Applications | Operations | Results | Publications | Imagery

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Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) evaluates growth of Leucine-rich repeat kinase 2 (LRRK2) protein crystals in microgravity. LRRK2 is implicated in Parkinson’s disease, but crystals of the protein grown on Earth are too small and compact to study. Detailed analysis of larger, space-grown crystals can define the protein’s exact shape and morphology and help scientists better understand the disease’s pathology.
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Information Pending

The following content was provided by Marco Baptista, Ph.D., Stefan Knapp, Ph.D., Sebastian Mathea, Ph.D., Susan Taylor, Ph.D., and is maintained in a database by the ISS Program Science Office.
Experiment Details

OpNom: PCG-16

Principal Investigator(s)
Marco Baptista, Ph.D., The Michael J. Fox Foundation, New York, NY, United States
Stefan Knapp, Ph.D., Goethe-University Frankfurt/Institute of Pharmaceutical Chemistry, Frankfurt, Germany
Sebastian Mathea, Ph.D., Goethe University Frankfurt, Frankfurt, Germany
Susan Taylor, Ph.D., University of California San Diego, La Jolla, CA, United States

Co-Investigator(s)/Collaborator(s)
Paul Reichert, M.S., Merck Research Laboratories, Kenilworth, NJ, United States

Developer(s)
The Michael J. Fox Foundation, New York, NY, United States
MiTeGen, LLC, Ithaca, NY, United States

Sponsoring Space Agency
National Aeronautics and Space Administration (NASA)

Sponsoring Organization
National Laboratory (NL)

Research Benefits
Information Pending

ISS Expedition Duration
October 2018 - March 2019

Expeditions Assigned
57/58

Previous Missions
A similar experiment with LRRK2 flew on SpX-12 under the name ‘CASIS PCG 7’. That experiment used the Microlytic Crystal Former Optimization Chip (16 Channel) hardware. While crystals were grown and successfully returned, they were of the same size and general quality as crystals grown on Earth. It is hoped that by using larger sample wells, having the crew fill the solutions on ISS as the investigator would in the lab and monitoring crystal growth on ISS, the crystals will be larger and of higher quality.

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Experiment Description

Research Overview

  • Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) grows Leucine-rich repeat kinase 2 (LRRK2) protein crystals in microgravity aboard the International Space Station (ISS).
  • The space-grown crystals are analyzed using x-ray diffraction and neutron diffraction studies upon return to Earth.
  • LRRK2 function is heightened in people with Parkinson’s disease and is associated with a mutation in the LRRK2 gene.
  • The results of the analysis provide researchers with a better detailed view of the crystalline structure of LRRK2. Development of inhibitor therapies targeting the LRRK2 protein may prevent, slow, or stop the progression of Parkinson’s disease.

Description

Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) may provide insight to Parkinson’s disease by observing microgravity-grown Leucine-rich repeat kinase 2 (LRRK2) protein crystal formations.
 
Parkinson’s disease (PD) is a chronic neurodegenerative disease that affects one in 100 people over the age of 60. It is estimated that approximately 1 million people have the disease in the United States and over 6 million worldwide. The disease is characterized by a slowness of movement, freezing of gait, and tremor along with many non-motor symptoms such as cognitive deficits, constipation, and depression.
 
The exact cause of PD is unknown but recently genetic studies have linked mutations in certain genes to an increase in PD risk. One example, is the Leucine-Rich Repeat Kinase 2 (LRRK2) where mutations on this gene represent one of the most common genetic risks for PD. Mutations in this gene cause an increase in LRRK2 activity that is detrimental to brain cells. There are now LRRK2 kinase inhibitors that have entered into clinical trials but the design of these drugs are being conducted without the knowledge of the structure of LRRK2. In a sense, it is like trying to make a key without knowing the details of the keyhole.
 
By solving the crystal structure of LRRK2, investigators may be able to provide important structural information to medicinal chemists to design better drugs against LRRK2. Crystal growth of LRRK2 on Earth is difficult and does not produce high quality crystals to ascertain high resolution atomic information. The intent of this investigation is to create superior quality of LRRK2 crystals in microgravity conditions, which allows for insight into what LRRK2 looks like. This may help drug researchers to make better medicine to treat PD patients.

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Applications

Space Applications
CASIS PCG 16 demonstrates use of the microgravity environment for researching and producing next-generation advances in biotechnology, potentially expanding interest in conducting scientific research on the space station.

Earth Applications
Defining the exact shape and morphology of LRRK2 using space-grown crystals could help scientists better understand the pathology of Parkinson’s and aid in development of therapies to prevent and treat the disease, which affects millions of people on Earth. The larger versions of proteins grown in space also may contribute to fundamental understanding of protein structure.

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Operations

Operational Requirements and Protocols
Hardware includes the Protein Crystal Growth Card MicroG and 1.5 mL Eppendorf tubes to hold the protein solution. The PCG Card MicroG is a modified version of a commercially available 96 well plate provided by MiTeGen. The precipitant solution is loaded into the PCG Card MicroG hardware prior to launch. The protein solution is loaded into Eppendorf tubes prior to launch. The PCG Card MicroG hardware launches at refrigerated temperature and the protein solution launches frozen. A crew member uses a pipette to transfer a drop of protein solution into the PCG Card MicroG protein reservoir and transfers a small volume of solution from the precipitant reservoir to the top of the protein drop to start the nucleation and crystallization process. Crystals are observed via microscope at 1, 4- and 20-days following filling. A second PCG Card MicroG is filled within 4-10 days prior to the end of the mission, followed by a final microscope session two days later. The PCG Card MicroG hardware is returned to Earth at refrigerated temperature for postflight analysis in the laboratory.

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Decadal Survey Recommendations

Information Pending

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Results/More Information

Information Pending

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Related Websites
Michael J. Fox Foundation

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Imagery

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NASA Image: ISS057E106231 - European Space Agency (ESA) astronaut Alexander Gerst uses a pipette to transfer a protein solution into the Protein Crystal Growth Card for an investigation observing protein crystals associated with Parkinson’s disease to potentially improve treatments on Earth. Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) evaluates growth of Leucine-rich repeat kinase 2 (LRRK2) protein crystals in microgravity. LRRK2 is implicated in Parkinson’s disease, but crystals of the protein grown on Earth are too small and compact to study. Detailed analysis of larger, space-grown crystals can define the protein’s exact shape and morphology and help scientists better understand the disease’s pathology.

+ View Larger Image


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NASA Image: ISS057E106417 - Samples from the Protein Crystal Growth Card are examined using a microscope for an investigation observing protein crystals associated with Parkinson’s disease to potentially improve treatments on Earth. Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) evaluates growth of Leucine-rich repeat kinase 2 (LRRK2) protein crystals in microgravity. LRRK2 is implicated in Parkinson’s disease, but crystals of the protein grown on Earth are too small and compact to study. Detailed analysis of larger, space-grown crystals can define the protein’s exact shape and morphology and help scientists better understand the disease’s pathology.

+ View Larger Image


image
NASA Image: ISS057E106419 - Samples from the Protein Crystal Growth Card are examined using a microscope for an investigation observing protein crystals associated with Parkinson’s disease to potentially improve treatments on Earth. Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) evaluates growth of Leucine-rich repeat kinase 2 (LRRK2) protein crystals in microgravity. LRRK2 is implicated in Parkinson’s disease, but crystals of the protein grown on Earth are too small and compact to study. Detailed analysis of larger, space-grown crystals can define the protein’s exact shape and morphology and help scientists better understand the disease’s pathology.

+ View Larger Image


image
NASA Image: ISS058E002064 - Crystallization of LRRK2 Under Microgravity Conditions-2 (CASIS PCG 16) floating in front of Window 7 in the Cupola module. Earth is in the background. CASIS PCG 16 evaluates growth of Leucine-rich repeat kinase 2 (LRRK2) protein crystals in microgravity. LRRK2 is implicated in Parkinson’s disease, but crystals of the protein grown on Earth are too small and compact to study. Detailed analysis of larger, space-grown crystals can define the protein’s exact shape and morphology and help scientists better understand the disease’s pathology.

+ View Larger Image