France

Capturing the rules governing developmental decisions in multicellular organisms is key to study cellular functions, including  reprogramming of cell differentiation and function. To understand how different genes coordinately regulate developmental decisions towards cell function, we used a multi-scale hybrid model integrating ordinary differential equations (ODEs) and agent-based modeling. This model allowed us to gain a deeper understanding in the coordinate function of key developmental genes, including WUSCHEL-RELATED HOMEOBOX 5 (WOX5) and SHORTROOT (SHR), to regulate stem cell divisions. We predicted cell-type-specific expression dynamics of SHR, SCARECROW, WOX5, AN3 and CYCLIND6;1, and showed an interdependency between CEI and QC divisions. At present, we know these stem cell populations divide, differentiate and display functions in response to relative positional information. A major challenge is to accurately capture the multicellular 3 dimensional (3D) microenvironment. To further study systemic behavior of these stem cells within a defined microenvironment, we established the framework of 3D bioprinting with plant cells to study cell viability, cell division, and cell identity. Within our designed microenvironment, the deposited Arabidopsis and soybean cells re-entered the cell cycle, which led to the formation of microcalli. Furthermore, we showed that the identity of isolated cells of Arabidopsis roots expressing endodermal markers maintained longer periods of time. We believe that the 3D bioprinting framework paves the way for a general use of 3D bioprinting for studying the rules governing developmental decisions.

SEB Annual Conference 2022

Coordinated regulation of gene expression among stem cells

Discover the art of creating extraordinary science at SEB’s Annual Conference at Le Corum Conference Center     in Montpellier, France from 5 to  8 July 2022.

SEB’s Annual Conference is celebrated for creating the perfect composition of research, new discoveries and collaborative connections. Be creative and innovative by exchanging ideas and knowledge with masters of biology from all over the world.

2022 will find over 1500 experimental biologists from across the globe converging on the third-largest French city near the Mediterranean coast and the fastest-growing city in the country over the past 25 years.
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Please register for the conference by clicking on this link:

https://www.sebiology.org/events/seb-annual-conference-2022/registration.html

The site will be open for registered participants closer to the event.

2022 will find over 1500 experimental biologists from across the globe converging on the third-largest French city near the Mediterranean coast and the fastest-growing city in the country over the past 25 years - Montpellier, France

technical paper

Like most research fields, biomimetic research has changed notably over the past centuries. However, successful biomimetic research has always been limited by available methods. Successful technological transfer of bio-inspired principles in aero- and hydrodynamics, materials sciences and structural and civil engineering involved traditional machining conventional manufacturing techniques. Only with recent developments in 3D printing, these fields have gained additional biomimetic interest. Improved and more affordable computational power have also increased computer based additional biomimetic research fields, such as bio-inspired neuronal networks and machine learning. In the past decades there have also been significant advances in the field of micro- and nanostructuring. Self-organizing surface modifications now allow to mass produce bio-inspired optical structures and other miniature topological features. The most recent advances in manufacturing technology however now start to push this limit even further and allow the full control of molecular assemblies of highly complex structures. The ability to assemble complex molecules might bring biomimetics to a whole new level - nano-biomimetics. This talk will discuss the possible role of nano-biomimetics and highlight how this exciting research field might allow to transfer biological principles from protein structures, molecular motors, cellular membranes and even extracellular matrixes into truly bio-inspired technological applications. 

Nano-biomimetics - the next step in bio-inspired research?!

Owls are a master to achieve silent flight in stealthy hunting or prey detection owing to their featured wing morphologies of leading-edge serrations, trail-edge fringes, and velvet-like surfaces. While the aeroacoustic characteristics of the owl-inspired leading-edge serrations has been a hot topic in terms of aerodynamic performance and noise suppression, their effects of serration-flexibility and passive deformation remain yet poorly studied. We have recently investigated experimentally the aerodynamic and acoustic performance of the propeller blades with both flexible and rigid serration-like appendages attached onto the blade tip. We utilized a high-speed camera system to measure the dynamic deformations of the serration-like structures and examined the aeroacoustic features of the various blades. Using three propeller blade models with the leading-edge (LE) serrations, we found that the flexible LE-serrated blade displays an optimal aeroacoustic performance with the high-frequency broadband noise suppressed remarkedly. Our results indicate that the flexible serrations with appropriate stiffness enable a pronounced sound reduction at high frequencies while sustaining the aerodynamic performance comparable to that of the non-serrated blades.

Effects of flexible owl-inspired serrations on aerodynamic performance and noise reduction

Deaf moths evade bat predation by reducing the amplitude of their echo signature. This has been achieved by evolving repeating structures on their wings which strongly absorb sound. The thickness of the wings are much thinner than the wavelengths they absorb, up to 1%, due to this subwavelength property moth wings can be classified as metamaterials. 
The purpose of this work is to profiteer from the bat-moth arms race and scale-up the metamaterial mechanism from ultrasound to audible frequencies. We design, build and test a moth-inspired acoustic absorbing panel which is tuned to within the human-hearing range that is extremely thin. In doing so, we also show that the biological mechanism can work at audible frequencies. As the target frequencies drop, the wavelengths increase, therefore the dimensions of the proposed metamaterial absorbing panel also increases. However, the proposed biomimetic absorbing panel (containing the moth-like repeating structure) is still extremely thin compared to the target frequency. This biomimetic sound absorber has the advantage of being as efficient as existing acoustic sound absorber panels but is significantly less thick. 








Subwavelength Bioinspired Acoustic Panels

Animal-legged locomotion is the result of tight interaction of biomechanics and neural control. Special focus has been set on multi-articulate coupling mechanisms; muscle-tendon networks that act simultaneously at multiple joints. Multi-articulate mechanisms are associated with joint movement coordination, reduction of forces and metabolic cost of transport, and even power amplification. Yet most multi-articulate configurations remain without sufficient functional explanation. In this presentation I will describe our latest projects in human- and bird-like locomotion, where we develop mechanical models (legged robots) featuring complex multi-articulate mechanisms. Our robots allow us to test the interaction of a complex leg design, with integrated neuromuscular-inspired control, and while locomotion in the physical world. Robots allow collecting rich biomechanical data from within: we measure joint angles, forces and torques, and electrical power consumption of motors. Already with simple control (feedforward) and a high degree of under-actuation (spring-tendon based function), we observe the emergence of natural-looking gaits. Specifically, our bird-inspired robot demonstrates a self-engaging and disengaging parallel leg elasticity that is switched through foot-ground contact. This is the first available proof where mechanical coupling between joint kinematics and function replaces neural coupling, to a large amount. We show that complex leg trajectories and leg function (stance leg, swing leg, and transitions) are established almost entirely through multi-articulate mechanical coupling, and with base-line control that mimics muscles isometric mode. We also show that our leg mechanism is theoretically scalable to dynamic loads and sizes of the largest animals ever roaming this world.

Mechanical joint coupling in an avian inspired legged robot

We all assume that physiological plasticity is advantageous because it allows organisms to respond to diverse or changing conditions. However, can being too plastic actually be detrimental? Malagasy common tenrecs, Tenrec ecaudatus, have many plesiomorphic traits and may represent an ancestral placental mammal. The physiology of these tenrecs is extraordinary. Tenrec body temperature (Tb) may approximate ambient temperature to as low as 12°C even when tenrecs are fully active. Conversely, tenrecs can hibernate with Tb of 28°C. During the active season, resting oxygen consumption may vary 25-fold with little or no change in Tb. We found that tenrecs essentially place homeostatic processes like kidney function on hold when metabolism is low much like a hibernator. In contrast to Boreoeutherian hibernators like ground squirrels, tenrecs are surprisingly intolerant of extremes in ambient temperature (&lt;8 or &gt;34°C). While plasticity may confer numerous energetic advantages in consistently moderate environments, environmental extremes may have limited the success and distribution of plastic basal mammals.

Physiological plasticity and the evolution of environmental tolerance in the common tenrec.

Thermal acclimation of some temperate fish species can stimulate changes in the physiological capacity of the heart. This is due to modifications to the active and passive properties of the myocardium. These modifications include changes in the Ca2+ sensitivity of the contractile element and to the amount and composition of myocardial collagen. Interestingly, this response is sex specific. Using cultured cardiac fibroblasts, from male and female trout, we have been working to determine how a change in physiological temperature leads to a change in deposited collagen. This work has integrated experiments examining the effect of biomechanical stretch, TGF-B, testosterone, angiotensin II, and microRNAs on the cell signalling pathways that regulate collagen deposition and turnover. We propose that increased biomechanical stimulation of the heart, caused by an increase in vascular resistance and blood viscosity, triggered by a decrease in physiological temperature, activates mitogen-activated protein kinase signalling pathways through stimulation of mechanosensitive membrane proteins and the release of TGF-B. The end result is changes in the expression of gene transcripts and cellular proteins that support an increase in collagen deposition including matrix metalloproteinases, and collagen monomers. It was also found that cellular pathways associated with the deposition of collagen are stimulated by physiologically relevant levels of testosterone, and that these can be reversed through the expression of microRNA-29b. These studies suggest that the phenotypic response of the heart to a change in environmental temperature is under complex regulatory control that is sex specific.  

Mechanotransduction and the regulation of collagen deposition by trout cardiac fibroblasts during thermal acclimation

The plant hormone gibberellin (GA) is involved in many developmental processes, however, how GA is distributed within plant tissues is not yet understood. In this talk, we present a multi-cellular mathematical model for GA transport within the Arabidopsis root. We consider both passive and facilitated modes of transport through the symplast and the apoplast. In particular, we model the effects of the NPF cytoplasm importers, localised in different layers of the root. In addition, we consider the effect of a vacuole as a possible storage mechanism for GA within each cell and model the role of transport across the tonoplast. We assume an effective GA source coming from the stele and constant degradation rate of GA within the whole root. We also present results on the values of the various transporter permeabilities, estimated from a model and oocyte experimental data. We discuss the governing equations and show numerical results predicting the spatial and temporal distribution of GA. Our results provide insights into the role of the vacuole in regulating the amount of GA in the cell, and how this contributes to GA distributions and cellular decision making.

Modelling GA transport within the Arabidopsis root

The hormone gibberellin (GA) controls plant growth and regulates growth responses to environmental stress. In roots and monocotyledonous leaves, GA controls growth by regulating the size of the division zone - regulating the cell's decision to cease division and begin rapid elongation. We used a systems approach to investigate the establishment of the GA distribution in the maize leaf growth zone to understand how drought and cold alter leaf growth. By developing and parameterizing a multiscale computational model that includes cell movement, growth-induced dilution and metabolic activities, we revealed that the GA distribution is predominantly determined by variations in GA metabolism. Considering wild-type and UBI::GA20-OX-1 leaves, the model predicted the peak in GA concentration, which has been shown to determine division-zone size. Drought and cold modified enzyme transcript levels, although the model revealed that this did not explain the observed GA distributions. Instead, the model predicted that GA distributions are also mediated by post-transcriptional modifications increasing the activity of GA20oxidase in drought and of GA2oxidase in cold, which we confirmed by enzyme activity measurements. This work provides a new, mechanistic understanding of the GA metabolism in plant growth regulation.

Modelling reveals post-transcriptional regulation of GA metabolism enzymes in response to drought and cold

During in vitro tissue culture, plants form callus and regenerate organs by reprograming developmental pathways. In addition to hormonal signals, stress-induced cues, such as those from wounding, can trigger and promote cellular reprogramming. Conjugation of the small ubiquitin-related modifier (SUMO) to target transcriptional regulators is thought to rapidly and precisely modulate their activity in response to stress. We previously investigated if SUMOylation is involved in wound-induced reprograming and showed that loss of the E3 ligase SIZ1 causes a hyper-active wound response and enhances shoot regeneration (Coleman et al, 2020). Based on these observations, we hypothesized that SUMOylation suppresses wounding-induced regulator(s) and searched for early acting players underlying the stress-induced cellular reprograming. By analyzing the transcriptome of wounded plants, we found that HEAT SHOCK FACTOR A1s (HSFA1s) are activated after wounding. Mutant and overexpression analysis showed that HSFA1s, also known to be activated by heat stress, promote shoot regeneration in Arabidopsis. Furthermore, the regulation of HSFA1s appeared independent of transcription and biochemical analysis revealed that they are subject to SUMOylation in response to stress. Here, I will discuss how key stress-induced transcription factors regulate cellular reprograming and how SUMOylation modulates this regenerative response in plants.

The role of SUMOylation during shoot regeneration in Arabidopsis

SUMO conjugation is emerging as an important mechanism to transduce environmental cues into cellular signaling. We present evidence to show that SUMOylation of key transcriptional regulators such as DELLA and BZR1, provides a conduit for environmental influence of root growth and development during salt stress. SUMOylation stabilizes BZR1 in the nucleus by inhibiting its interaction with BIN2 kinase. During salt stress, Arabidopsis plants arrest growth through deSUMOylation of BZR1 in the cytoplasm by promoting the accumulation of the BZR1 targeting SUMO protease, ULP1a. ULP1a mutants are salt tolerant and insensitive to the BR inhibitor, brassinazole with regards to root growth. BR treatment stimulates ULP1a degradation, allowing SUMOylated BZR1 to accumulate and promote growth. This study uncovers a mechanism for integrating environmental cues into BR signaling to shape root growth.
Intriguingly an interacting partner of BZR1, the growth repressing DELLA proteins are also SUMOylated. We demonstrate that a proportion of DELLAs are conjugated to SUMO, the extent of conjugation increases during salt stress. We identify a SUMO interacting motif (SIM) in the GA receptor GID1 and demonstrate that SUMO-conjugated DELLA binds to this motif in a GA-independent manner. The consequent sequestration of GID1 by SUMO-conjugated DELLAs leads to an accumulation of non-SUMOylated DELLAs resulting in repression of root growth in salinity.  We present a model depicting how SUMO decodes environmental cues to shape root growth and development. 

Coordinated regulation of gene expression among stem cells

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