Ready for Our Trip to Mars? Turning the Red Planet Blue

Mars exploration is one of the major current scientific breakthroughs. NASA is actively developing its Mars Exploration Program through several rovers and orbiters to better understand the origin and current conditions of the Red Planet. Since Mars is more Earth-like than any other planet, understanding its formation and evolution could enable to better understand our own origin. Mars is also considered as a future destination for survival of humankind, assuming our ability to face remaining technical challenges, such as radiation risks, extreme conditions, food and medicine supplies. The recent evidence of liquid water on Mars suggests that life could exist, and will be seeked by NASA Mars 2020 rover. Thus, Mars exploration opens remarkable perspectives towards the discovery of new resources and the humanity's expansion. But this tremendous potential also implies completely new questions: what will happen to the Earth if humans are able to escape from global warming and pollution? How will the Martian land be shared between Nations? Will it be impacted by political conflicts on the Earth? If life exists on Mars, will it be compatible with humans? As we get closer to Mars colonization every day, these questions should be addressed and considered as a new chance to envision a world that could benefit from the lessons of History. So, in addition to technical and scientific progress, Mars exploration gives us the chance to redefine our society as a whole

Predicting Cell Death and Mutation Frequency for a Wide Spectrum of LET by Assuming DNA Break Clustering Inside Repair Domains

Cosmic radiation, which is composed of high charged and energy (HZE) particles, is responsible for cell death and mutation, which may be involved in cancer induction. Mutations are consequences of mis-repaired DNA breaks especially double-strand breaks (DSBs) that induce inter- and intra-chromosomal rearrangements (translocations, deletions, inversion). In this study, a computer simulation model is used to investigate the clustering of DSBs in repair domains, previously evidenced by our group in human breast cells [1]. This model is calibrated with experimental data measuring persistent 53BP1 radiation-induced foci (RIF) and is used to explain the high relative biological effectiveness (RBE) of HZE for both cell death and DNA mutation frequencies. We first validate our DSB cluster model using a new track structure model deployed on a simple geometrical configuration for repair domains in the nucleus; then we extend the scope from cell death to mutation induction. This work suggests that mechanism based on DSB repair process can explain several biological effects induced by HZE particles on different type of living cell

53BP1 Repair Kinetics for Prediction of In Vivo Radiation Susceptibility in 15 Mouse Strains

International audienceWe present a novel mathematical formalism to predict the kinetics of DNA damage repair after exposure to both low- and high-LET radiation (X rays; 350 MeV/n 40Ar; 600 MeV/n 56Fe). Our method is based on monitoring DNA damage repair protein 53BP1 that forms radiation-induced foci (RIF) at locations of DNA double-strand breaks (DSB) in the nucleus and comparing its expression in primary skin fibroblasts isolated from 15 mice strains. We previously reported strong evidence for clustering of nearby DSB into single repair units as opposed to the classic “contact-first” model where DSB are considered immobile. Here we apply this clustering model to evaluate the number of remaining RIF over time. We also show that the newly introduced kinetic metrics can be used as surrogate biomarkers for in vivo radiation toxicity, with potential applications in radiotherapy and human space exploration. In particular, we observed an association between the characteristic time constant of RIF repair measured in vitro and survival levels of immune cells collected from irradiated mice. Moreover, the speed of DNA damage repair correlated not only with radiation-induced cellular survival in vivo, but also with spontaneous cancer incidence data collected from the Mouse Tumor Biology database, suggesting a relationship between the efficiency of DSB repair after irradiation and cancer risk

Particle Separation with Deterministic Lateral Displacement (DLD): The Anisotropy Effect

Deterministic lateral displacement (DLD) is a passive and label-free microfluidic separation technique with a strong potential for biological sample preparation purposes. Numerical and experimental models have been proposed so far to predict the particle behavior in DLD channels. However, they do not take into account the influence of the pillar anisotropy that induces a secondary pressure gradient in the direction perpendicular to the main flow. The influence of the pillar geometry on the anisotropy magnitude is presented. We show that anisotropy impacts the trajectory of particles in DLD devices and should be included in predictive models for the critical diameter

In Situ Detection of Complex DNA Damage Using Microscopy: A Rough Road Ahead

Complexity of DNA damage is considered currently one if not the primary instigator of biological responses and determinant of short and long-term effects in organisms and their offspring. In this review, we focus on the detection of complex (clustered) DNA damage (CDD) induced for example by ionizing radiation (IR) and in some cases by high oxidative stress. We perform a short historical perspective in the field, emphasizing the microscopy-based techniques and methodologies for the detection of CDD at the cellular level. We extend this analysis on the pertaining methodology of surrogate protein markers of CDD (foci) colocalization and provide a unique synthesis of imaging parameters, software, and different types of microscopy used. Last but not least, we critically discuss the main advances and necessary future direction for the better detection of CDD, with important outcomes in biological and clinical setups

Anticipating Cutoff Diameters in Deterministic Lateral Displacement (DLD) Microfluidic Devices for an Optimized Particle Separation

International audienceDeterministic lateral displacement (DLD) devices enable to separate nanometer to micrometer-sized particles around a cutoff diameter, during their transport through a microfluidic channel with slanted rows of pillars. In order to design appropriate DLD geometries for specific separation sizes, robust models are required to anticipate the value of the cutoff diameter. So far, the proposed models result in a single cutoff diameter for a given DLD geometry. This paper shows that the cutoff diameter actually varies along the DLD channel, especially in narrow pillar arrays. Experimental and numerical results reveal that the variation of the cutoff diameter is induced by boundary effects at the channel side walls, called the wall effect. The wall effect generates unexpected particle trajectories that may compromise the separation efficiency. In order to anticipate the wall effect when designing DLD devices, a predictive model is proposed in this work and has been validated experimentally. In addition to the usual geometrical parameters, a new parameter, the number of pillars in the channel cross dimension, is considered in this model to investigate its influence on the particle trajectories

Separation of Biological Particles in a Modular Platform of Cascaded Deterministic Lateral Displacement Modules

Abstract Deterministic lateral displacement (DLD) has been extensively implemented in the last decade for size-based sample preparation, owing to its high separation performances for a wide range of particle dimensions. However, separating particles from 1 μm to 10 μm in one single DLD device is challenging because of the required diversity of pillar dimensions and inherent fabrication issues. This paper presents an alternative approach to achieve the extraction of E. coli bacteria from blood samples spiked with prostate cancer cells. Our approach consists in cascading individual DLD devices in a single automated platform, using flexible chambers that successively collect and inject the sample between each DLD stage without any external sample manipulation. Operating DLD separations independently enables to maximize the sorting efficiency at each step, without any disturbance from downstream stages. The proposed two-step automated protocol is applied to the separation of three types of components (bacteria, blood particles and cancer cells), with a depletion yield of 100% for cancer cells and 93% for red blood cells. This cascaded approach is presented for the first time with two DLD modules and is upscalable to improve the dynamic range of currently available DLD devices