Why is our immune system confused during space flight? Searching for mechanisms that modulate T cell activity in response to space stressors

Deyhle Jr. Richard

Promoter

Baatout Sarah, sbaatout@SCKCEN.BE

SCK•CEN Mentor

Moreels Marjan
marjan.moreels@sckcen.be
+32 14 33 28 16

SCK•CEN Co-mentor

Baselet Bjorn
bjorn.baselet@sckcen.be
+32 14 33 21 42

Expert group

Radiobiology

PhD started

2018-01-15

Short project description

Space travel comprises a unique and complex stress model composed of physical (i.e. radiation and microgravity) and psychological stressors. These extreme conditions can induce specific responses in the human body that will ultimately affect several organ systems. The precise nature of these health effects is not completely understood, and multiple underlying causes might be involved. In view of future interplanetary travel, studies onboard the International Space station (ISS) will help to answer many critical questions. Next to flight studies, the European Space Agency (ESA) offers a number of ground-based programmes for researchers to test theories without launching experiments into space. Currently, the Radiobiology Unit of SCK•CEN is involved in six ESA accepted in-flight ISS studies, as well as multiple ground-based in vitro and in vivo experiments using space flight analogues.

Alterations of the immune system are considered particularly important for the success of long-term, exploratory-type human space missions. Our past and current research involving space flight experiments and in vivo space analogs on Earth (e.g. bed rest, Antarctica winter-overs) indicate a strong impact of space flight stressors on the immune system. However, the direction of such alterations may appear contradictory, with some data indicating depressed immune responses, while other experiments point towards an up-regulated immune activity. Indeed, the impact of the different space stressors on an appropriate immune response in space is not well understood. In addition, in vitro experiments performed at the Radiobiology Unit revealed that immune cells suffer numerous molecular and cellular changes when exposed to simulated space conditions (radiation and/or microgravity and /or stress hormones). Importantly, there are reasons to believe that T cells, a key player in the cell-mediated immunity, are particularly affected by space stressors. Thus, investigating how T cells react to the different space stressors (either combined or in isolation) seems critical to understand the space-induced immune dysfunction.

Objective

The main objective of this PhD project is to investigate how T cells, key regulators in the cellular immune response, are affected by factors associated with the spaceflight environment (microgravity, radiation, psychological stress). A specific focus will be placed on further elucidating the signaling pathways that control T cell alterations to space flight stressors using both in vitro and in vivo models.

A second purpose of this PhD project is to develop effective countermeasures to preserve T cell activity, hence cellular immunity during space flight conditions. Thus, beyond the obvious space-related applications, the results delivered by this project could have clinical significance for patients suffering from immune disorders on Earth.

To achieve the objectives described above, the PhD candidate will use in-flight experiments on board the ISS as well as space-analogue models (e.g. Antarctic expeditions, bed rest), as a platform to analyse T cell behavior. In addition, in vitro ground-based experiments using space simulating devices will be performed at SCK•CEN. For the latter, two Random Positioning Machines are available at the Radiobiology Unit. In order to simulate cosmic radiation, experiments with low-linear energy transfer (LET) photons or high-LET neutrons can be performed at the irradiation facility available at SCK•CEN. Moreover, we will apply for high-LET beam time at international accelerator facilities (GANIL, GSI, iThemba …). Psychological stress can be mimicked by adding different stress hormones (e.g. cortisol) to cell cultures.

To investigate the molecular events behind T cell alterations to space stressors, various immune parameters will be analyzed using high-throughput technologies available within the genomic and Luminex platform at SCK•CEN: whole genome analysis of T cells, standardized monitoring of the overall immune status using the in vitro delayed-type hypersensitivity test, high-throughput quantitative analysis of inflammatory proteins (cytokines) using the Luminex Technology.