Space mission experiments part 1: conducting remote tests and the effect of staying in space on the immune system

Review of scientific experiments and technological demonstrations that will be carried out by Eitan Stiva in the sky mission. Out of 31 missions approved. Review First in the series

Eitan Stiva, who will fly to the International Space Station, will perform 31 experiments in the sky operation. Most of them - 24 are in the field of medicine. We hereby bring the first part detailing the experiments that Stiva will conduct in the medical field.

1. CRISPR-based diagnosis of viruses and bacteria in space missions

Diagnosis at the genetic level is a powerful tool for the precise identification of viruses, bacteria, and even specific genes, for example those that confer resistance to antibiotics. CRISPR systems are best known for their ability to be used for genetic editing, a discovery for which the Nobel Prize in Chemistry was awarded in 2020. However, these systems can also be used for simple and fast genetic diagnosis while maintaining high specificity. Because CRISPR systems are extremely compact and require no special expertise or equipment, they may be well suited for use on long-duration space missions, such as on the International Space Station or future missions to explore the Moon and Mars. In this experiment we will test different components of this diagnostic technology in microgravity conditions on the International Space Station. We hope that it will be possible to use the CRISPR systems for accurate diagnostics of bacteria and viruses that may attack crew members in space missions, and in the future even to diagnose diseases in space agriculture.

Principal Investigators: Dr. Dodo Burstein, Tel Aviv University and Dr. Gore Pines, Volcanic Institute.

2. Spacetravel - multidimensional examination of T cells in space conditions to improve the immune system

Disruption of the immune system function of spaceflights is one of the physiological consequences of being in microgravity conditions on the human body. The disorder may cause both an overactivity of the immune system - which is manifested in various allergy symptoms, and a decrease in immune activity which may lead to a renewed outbreak of dormant viral infections - and for example, the outbreak of cold sores in the cavity is common.

With a desire to understand the nature of the disorder in space, the researchers are leveraging the technological breakthroughs in providing personalized medicine. OncoHost, an Israeli startup, develops a platform to help choose the appropriate treatment for oncology patients according to their personal characteristics, and through the use of advanced technologies and machine learning algorithms and provides a multidimensional analysis of each patient's immune system. The advanced processing tools of the OncoHost platform will allow an analysis of the specific effects of the stay in space on the immune system of each astronaut.

These insights will enable the development of appropriate countermeasures to prevent and respond to life-threatening conditions along the journeys of deep space exploration missions. In addition, proving the valuable potential in characterizing people's immune systems to provide tailored treatment is expected to ignite a new phase in the provision of personalized clinical solutions and benefit humans - both in space and on Earth.

This trial is part of the clinical studies that will be performed on members of the AX1 team.

main investigator: Prof. Jacob Lawrence, Sheba Medical Center.

Affiliates: Thomas Jefferson University, USA and the Israeli start-up company OncoHost.

The Human BBB In Space 3: The effect of space flight and exposure to microgravity on the blood-brain barrier as a possible platform for the treatment of Alzheimer's

Normal functioning of the brain cells is necessary for the functioning of the body. In order to protect the sensitive brain tissue, the walls of the blood vessels that supply the brain are wrapped in a unique tissue that prevents the entry of toxic substances and infections from the blood into the brain, and enables the removal of waste from the brain to the blood - called the Blood-Brain-Barrier. Impairment of barrier functions is linked to the development of neurodegenerative diseases, such as Alzheimer's. In addition, the barrier poses a clinical challenge - as it prevents the passage of drugs from the blood to the brain tissue, which are required to treat neurodegenerative diseases.

In the study, the Sheba Medical Center researchers want to examine whether exposure to the microgravity conditions in space leads to a change in the function of the blood-brain barrier. The flights to space will undergo advanced non-invasive tests - advanced processing protocols of the results of brain MRI scans and the extraction of protein markers from blood tests before and after the flight, which will allow for the demonstration of the changes that have occurred in the function of the barrier as a result of the journey in space and the stay in microgravity conditions. The insights expected to be gained from the groundbreaking research will help in the development of abilities to influence the function of the barrier and the passage of materials through it - both in the removal of toxic waste proteins and the introduction of drugs. Abilities that will enable the treatment of Alzheimer's and other neurodegenerative diseases, and will help many patients around the world.

This trial is part of the clinical studies that will be performed on members of the AX1 team. 

Principal Investigators: Dr. Itzik Koper, PhD, Director of the Blood Brain Barrier Group at the Yosef Segol Center for Neuroscience, Sheba Medical Center and Prof. Yael Mardor, Chief Scientist and Head of the Magnetic Imaging (MR) Research Group of the Institute for Advanced Technologies at the Sheba Medical Center.

4. Urinalysis in Space - performing a urine test and analyzing the results in real time on the space station 

As space missions become longer and more common, the astronauts on them will need a variety of diagnostic tools to monitor body functions, including urine testing. Analysis of urine samples is used as a standard method for testing various health conditions, from characterizing metabolic processes to kidney function. Kidney function in space is a researched topic. However, previous studies have involved capturing urine in space and testing it back on Earth. The proposal focuses on performing the ACR test - ratio between albumin and creatinine - a urine test in space, which allows astronauts to measure kidney function in real time independently. 

main investigator: Healthy.io.

5. Impact of Space-Travels on the Urinary Microbiome: Examining the impact of space travel on a change in the microbiome population of the urinary tract and its clinical implications

As part of this experiment, the research clinicians at Sheba Medical Center, at Thomas Jefferson University, and other partner researchers, will examine the changes in the population of microorganisms inhabiting the urinary tracts ("urinary microbiome") of the AX-1 mission team, throughout all stages of their journey to the International Space Station - before The launch, during the journey, and after returning to Earth.

Through the use of genetic analysis tools and advanced algorithms of the MicroGenDX company, along with cross-referencing the analysis findings with various clinical symptoms during the mission, the research team will for the first time provide insights into the correlation between the characteristics of the microbiome in the urinary tract and the appearance of symptoms and disease states. These insights will allow a breakthrough in understanding the clinical relationship between the microbiome population and the health of the urinary system, and will enable the provision of adequate medical care - both for mission teams in space and for patients on the ground.

This trial is part of the clinical studies that will be performed on members of the AX1 team. 

Principal Investigators: Dr. Ben Brossi, Oncology Center, Sheba Medical Center and Dr. Paul Chang, Urology Department at Thomas Jefferson University Hospital, USA.Affiliates: Thomas Jefferson University Hospital, Pennsylvania, USA, Texas Tech University, Texas, USA, Queens University Hospital, Ontario, Canada, and with the support of MicroGenDx, Texas, USA.

For the rest of the series:

5. Characterization of the changes that occur in cancer cells under microgravity conditions in space, with the aim of developing innovative treatments for leukemia in children 

Leukemia is the most common cancer in children, requiring prolonged and aggressive treatment. The treatment available today is effective in most cases, but its effectiveness comes at the cost of high toxicity, which causes short and long-term side effects. In order to find an alternative to the existing treatments, the hematological-oncology setup at the Schneider Center decided to test the effect of microgravity conditions on T-type acute lymphoblastic leukemia cells, by sending the cells into space in a tiny laboratory. The findings of the experiment will be compared to an identical experiment that will be conducted on Earth, while monitoring the changes in gene expression in the cells. Since preliminary experiments in microgravity conditions showed hypersensitivity to cancer cells, the results of the study can contribute to the understanding of cellular mechanisms affected by microgravity. This understanding will help the way in which innovative treatments will be developed that can provide a therapeutic response to aggressive and resistant cancers, and reduce the side effects of the currently accepted treatments. The experiment will be done with the integration and participation of children treated in the hematological-oncology unit at the Schneider Center.

Principal investigator: Dr. Judit Birger, the hematological-oncology department at the Schneider Pediatric Center.

Affiliates: The Educational Center at the Schneider Center, Felzenstein Research Institute, Tel Aviv University, Spice Pharma Company.

: SpacePharma, Space Applications.

6. The effect of space flight on the cardiovascular health of the astronauts

The absence of gravity in space changes the structure of the heart and the size of the heart chambers. In addition, exposure to space radiation may accelerate the progression of arteriosclerosis and even cause calcification in the blood vessels. That's why candidates for space flight must perform comprehensive tests of the cardiovascular system, and we have already gained experience with this.

Innovative molecular technologies allow us to identify different health conditions in the human body. Through a thorough examination of biological samples (blood, saliva, urine and feces), we discovered that a significant percentage of the biological substances (metabolites) found in the bloodstream are a unique product of bacteria from the microbiome (all the bacteria inhabiting the human body found in the digestive tract). The microbiome changes following a stay in space and nutritional changes in space, and as a result we expect that the metabolites in the blood of the astronauts flying into space will also change. 

In recent years we have created one of the largest databases in the world of heart patients and compared to healthy people. Using mathematical models and machine learning, we characterized metabolic pathways mediated by intestinal bacteria and related to the cardiovascular system that were not known until now. In a study currently being conducted by the Billinson Hospital in collaboration with the Weizmann Institute, we will investigate the same metabolic pathways in the astronauts that we discovered in "normal" people who do not fly into space. Our research plan is to build an accurate personal metabolic map for each astronaut based on the microbiome and metabolites from biological samples that we will collect from the astronauts at different time points before and after the flight. This metabolic map will allow us to assess the change in cardiovascular risk for each astronaut following a space flight and thus understand more comprehensively and precisely the effect of being in space on the cardiovascular system. This is pioneering and groundbreaking research and we are happy for the opportunity we have been given to cooperate with the "Rakia" project and the second Israeli in space - the pilot Eitan Stiva.

This experiment is not included in the list of experiments selected by the voice of the reader in May 2021, but was approved and added by the scientific and technological committee in September 2021 due to its importance and contribution to comprehensive research at the hospital. This trial is part of the clinical studies that will be performed on members of the AX1 team.

Principal Investigators: Prof. Ran Kornovsky, Dr. Yala Telmore-Barkan, Prof. Eran Segal, Dr. Itamar Mehul.

7. Gene Expression - characterization of the genetic expression mechanism underlying the effect of space conditions on an increase in the violence of disease-causing bacteria

Salmonella enterica bacteria, common pathogens that cause diseases in humans and animals, are one of the main causes of food poisoning in Israel and around the world. Previous studies, including an experiment conducted by a team of researchers from Sheba, found that under microgravity conditions there is a significant increase in the bacteria's ability to cause significant morbidity - through an increase in their mechanisms of violence and an improvement in their resistance to antibiotics. Understanding the mechanisms that underlie the phenomenon is required in order to develop appropriate medical treatments, and to deal with morbidity and the increase in bacterial resistance to current antibiotic treatments.

Rakei's mission is an extraordinary opportunity to continue researching the subject. As part of the research, disease-causing bacterial cultures will be grown in space, and identical cultures will be grown at the same time on Earth. The researchers of the Center for Infectious Diseases at the Sheba Medical Center will compare various characteristics between the cultures - such as the differences in the rate and manner of growth between the pathogen cultures, alongside the analysis of the changes that have occurred in the genetic expression that underlies the increase in the violence of the bacteria. Thus, the insights from this study are expected to provide significant information about the mechanisms leading to the increase in the violence of bacteria, and to assist in the development of ways of dealing with and treatments against the morbidity caused by these pathogens.

This experiment is an integral part of the 'Sky' mission and passed the secondary and safety surveys, but due to technological gaps, the experiment is planned to be carried out on the space station in May 2022 as part of the Spx-25 cargo flight and is accompanied by a Sky mission.

main investigator: Prof. Ohad Gal-Mor, Center for Infectious Diseases at Shiba Tel Hashomer.

More of the topic in Hayadan:

• Cardiosense, Ultrasight and Monfort are sending products to Eitan Stiva's space mission
• Three experiments from the Technion will be launched to the International Space Station
• "Eitan Stiva takes the startup nation into space with him"
• Researchers have grown a human blood-brain barrier outside the body, in a way that makes it possible to predict the penetration of drugs into the brain in a customized way