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The Cell and Gene Therapy Catapult is one of a network of elite technology and innovation centres established by Innovate UK. Applying business-led research, Catapults help businesses transform great ideas into valuable products and services to compete in the global markets of tomorrow.
This keynote presentation will share valuable insight into sector skills challenges in one of the most novel and exciting industries, and explain how the Cell and Gene Therapy Catapult, through an ongoing effort to harness powerful collaborations, has devised and implemented a successful, award-winning training system including the Advanced Therapy Apprenticeship Community programme and an Online Training Platform to address these.


SEB Conference Prague 2024

Collaboration and Training for the Future of Advanced Therapies: The Cell and Gene Therapy Catapult

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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.

Fishes that tolerate salinities above 60 ppt (hypersaline saltwater) appear to use largely similar, but exaggerated, mechanisms as during standard seawater acclimation (~32-35 ppt). One unique aspect of hypersaline saltwater acclimation is further gill cell junction tightening to retain water while maintaining high paracellular Na+ export. The upregulation of “hypersalinity-specific” tight junction paralogs (i.e., claudin 10c and 10f) has been associated with this change in gill permeability in the Common Killifish (Fundulus heteroclitus). Here, we further test the hypothesis that these paralogs contribute to high hypersaline saltwater tolerance in F. heteroclitus by comparing their responses to the Banded Killifish (F. diaphanus), a less-tolerant congener, and their natural F1 hybrids (F. diaphanus × F. heteroclitus). As predicted, proxies of iono- (plasma [Na+, Cl- and K+]) and osmoregulatory homeostasis (muscle water content) suggest F. heteroclitus has a higher tolerance to 60 ppt than F. diaphanus, while F1 hybrids have intermediate tolerance. At the molecular level, only F. heteroclitus significantly upregulated total relative Claudin 10c and 10f mRNA content in the gill after 24 hours at 60 ppt. To study Claudin 10c regulation, we measured allele-specific expression in F1 hybrids. The mRNA content of the F. heteroclitus allele matched F. diaphanus at 10 ppt, but was 2-fold higher at 60 ppt, suggesting that cis-regulatory evolution has led to the hypersalinity-induced increase of Claudin 10c in F. heteroclitus. These data support the hypothesis that hypersalinity specific, cation selective tight junction paralogs contribute to the evolution of extreme hypersalinity tolerance in fishes.

Cis-regulated claudin 10c expression in gill is associated with variation in hypersaline seawater tolerance among species of killifish (Fundulus spp.)

Blackwater systems, characterized by low pH, low ion concentrations, and a high concentration of dissolved organic carbon (DOC) are found globally. The most notable are the blackwaters of the Amazon River, one of the most biodiverse ecosystems worldwide. The harsh water chemistry is toxic to most freshwater fish, while endemic species including the dwarf cichlid, thrive due to the protective effects provided by DOC. Natural DOCs were collected in the Amazon basin: a DOC-rich, low pH, ion-poor “blackwater” from the Rio Negro and a water lower in DOC but higher in pH and ion concentration from the Rio Solimoes. Due to the complexity and heterogeneity of DOCs, three model compounds; tannic acid, bovine serum albumin and sodium dodecyl sulfate, with known chemical properties were chosen based on the criteria that they structurally resemble or functionally behave like certain chemical moieties of humic acid, a major component of natural DOCs. Dwarf cichlids were exposed to control water, or one of the five DOCs at pH 7 or pH 4 and net Na+ and Cl- fluxes, ammonia-N and urea-N excretion rates and gill paracellular permeability were measured. Our results demonstrate that the effects of the natural DOCs are related to their chemical structure and water pH. This contributes to understanding the properties of DOC that are interacting with the gill and how this interaction influences ion and water transport in acidic waters (NSERC, ADAPTA, CNPQ). 



The protective ionoregulatory effects of dissolved organic carbon (DOC) and model compounds in a native Amazonian fish, the dwarf cichlid (Apistogramma agassizii).

Muscle properties such as strength and stiffness vary between species, joints, and age groups, but how these parameters interact to affect locomotor performance can be difficult to assess in complex models. To address this issue, we developed a simplified model of a single joint with two antagonistic Hill-type muscles, and varied the associated muscle parameters combinatorially over a large range. For a given parameter combination, we found optimal joint movements that minimized movement time while starting and ending at rest. The reduction of force, maximum contraction velocity and activation rate all had detrimental effects on performance, independent of other parameters. In contrast, over the large parameter space, deactivation and passive stiffness had no effect on performance on their own, but pronounced interactive effects with eachother. Increasing stiffness reduced joint movement time at fast deactivation rates, but increased movement time at low deactivation rates. This occurs because antagonist muscles resist the passive tension at rest, but are stretched eccentrically by the agonist, amplifying their active resistive force. Fast-deactivating muscles can avoid this resistive effect, allowing the passive stiffness to amplify accelerating force and enhance performance. Our results suggest that ameliorating muscle deactivation with age could be explored as a potential therapeutic target to enhance rapid motion, and that fast deactivation of muscle may be an important functional trait in animals using ballistic movements.

Interaction of muscle parameters on ballistic joint movement - implications for ageing and comparative locomotion

A muscle’s physiological properties determine its force-length (F-L) and force-velocity (F-V) relationships, and thus the fibre length and contraction speed at which maximal force and power can be produced. Here, we investigated the relationship between F-L and F-V relationships and in vivo muscle function in the guinea fowl (Numida Meleagris) main ankle extensor, the lateral gastrocnemius (LG) muscle during walking and running. To do so, we map each individual birds’ in vivo work loops to their individual force-length and force-velocity relationships. We hypothesize that muscles operate near optimal conditions for force and power production, respectively, during walking and running tasks to optimize efficiency during locomotion. We found that force development occurs entirely on the ascending limb of the F-L relationships curve in both walking and running and thus not at lengths that would maximize force output. LG muscles operate at low velocities at peak force and at optimal intermediate velocities during lower forces. These in vivo LG velocities are consistent with optimizing force and power according to the F-V relationship. Hence, a muscle’s operating length and velocity are not solely driven by efficiency. A potential explanation is that muscles act on the ascending limb of the F-L relationship to improve robustness against perturbations. We are currently performing model-based simulations of guinea fowl locomotion to explore how a muscle’s physiological properties affect its operating length and velocity. Our central hypothesis is that we will need to account for robustness against uncertainty in the simulations to capture the experimentally observed relationship.

Relating in vivo muscle dynamics to force-length-velocity relationships: from experiments to musculoskeletal models

Competition over rare and limited resources is an important evolutionary driver of behaviour. One such resource found in nature are carrion carcasses, which the burying beetle Nicrophorus vespilloides depends on to breed. However, these carcasses are highly valuable and often bring these beetles into competition with other species, including opportunistic vertebrate scavengers. While we might predict the beetles should have some mechanism to deal with these encounters, little is known about how such interactions inform parental care decisions of N. vespilloides. Here, we test whether this includes facultative adjustments to parental care. We found that parents were slower to return to providing care when given cues that indicated vertebrate scavengers were present. Despite this, we found there was no difference in the overall amount of care parents provided, or in resulting larval fitness. Our results are consistent with previous work that shows while vertebrate competition does trigger a strong immediate response in these beetles, any long-term adjustments in parental behaviour are limited. This suggests that the selective pressure for long-term adjustments here is weak, and we find evidence that these beetles may instead rely on non-facultative behaviours such as concealing carrion to deal with asymmetric competition.

Competition with vertebrate scavengers' delays return to parental care in the burying beetle Nicrophorus vespilloides

Camouflaging strategies in animals primarily includes the efficient feature to merge with the background of the ecosystem. This physiological phenomenon is an evolutionary process regulated by specific genes and is effective in terms of prey-predation equation. The colouration mechanisms in animals comprehends sophisticated pigment physiology, which is exhibited in a proficient way on the body surface of the animal to conflate with the adjacent environment. This work uses a semi-transparent freshwater prawn species, Macrobrachium lamarrei, to elucidate the mechanism to camouflage in the aquatic medium thus using the light intensity underwater. Macrobrachium lamarrei has specific arrangement of pigment droplets on its exoskeleton. However, the exclusivity of camouflage exists within the semi-transparent appearance of the body, for which, the organism effectively becomes ‘invisible’ in the aquatic habitat. The accumulative effects of semi-transparency and pigment droplet distribution on the body surface, plays the crucial role in the hiding strategy. In fact, the degree of semi-transparency is regulated by the organism and the intensity of light plays a critical role in the reflection of the image of the prawns to the predator. This study is conceptualised on the interplay of light and transparency where we have used a semi-transparent aquatic organism as a reliable biophysical model to analyse camouflagic adaptation.

Semi-transparency: Strategic camouflaging technique in a freshwater prawn

Escape responses in schooling fish have been researched at length, though little is known regarding how responses may differ as schooling fish grow. To investigate this, we elicited escape responses in a subset of individuals from schools (consisting of 20 individuals) of different size ranges of shiner perch (Cymatogaster aggregata), by triggering a visual stimulus when 3-6 individuals were positioned l within view of the stimulus, with their resulting reaction to a threat ensuing further responses across the rest of school which could not see the stimulus because of an opaque barrier that was suspended above the water level. We analysed individual turning rates, latencies, and the propagation of the reaction among individuals. Our experiments revealed distinct patterns in response behaviour: as expected, turning rate decreased with fish size. Conversely, these smaller individuals exhibited longer latencies in initiating the escape response, suggesting a trade-off between speed of turning and reaction time across sizes. Furthermore, size was found to significantly affect the spread of information among individuals that detected the escape-triggering stimulus, with larger individuals facilitating faster propagation of the response throughout the school. These findings highlight the complex interplay between individual size and collective behaviour in fish schools, suggesting that size not only influences individual escape performance but also the efficiency of information transfer within groups. Our results contribute to a deeper understanding of the mechanisms underpinning escape responses in gregarious fishes, with implications for the study of predator-prey interactions and the evolutionary dynamics of schooling behaviour.

The effect of fish size on the escape responses of schooling shiner perch Cymatogaster aggregata

Insect auditory transduction occurs within a scolopidium—a multicellular unit comprised of one or two auditory neurons enclosed in a supporting cell called the scolopale cell. In a tympanic ear, the apical end of the scolopidium is embedded in a cap cell that connects the scolopidium in series to the tympanum. The mechanism by which vibrations at the tympanum elicit the transducing current in the scolopidium remains highly speculative due to the absence of direct observation of sound-evoked motion in the scolopidium. In this study, we examined scolopidia from auditory neurons in ex-vivo preparations of Müller’s organ obtained from the desert locust, Schistocerca gregaria. We used Optical Coherence Tomography (OCT) to characterize background motions of Müller’s organ in the region where the scolopidia is located. Subsequently, we employed a CMOS-based high-photon efficiency (capturing 95% of photons), high-speed camera to characterize the relative motion within the scolopidium at about ten thousand frames per second in response to sound stimulation from 1 to 5 kHz. The characterization of the relative motion within the scolopidium was achieved by subtracting the background motion of Müller’s organ using image processing techniques. The obtained characterization reveals the complex motions of Müller’s organ itself and that of the scolopidium, implicating the role of these motions in locust auditory transduction. Additionally, we propose a possible gating mechanism of insect auditory transduction based on these observations.

Characterizing time-resolved motion within the scolopidium and its role in the gating mechanism of insect auditory transduction

Marine and aquatic environmental fluctuations in temperature, salinity, oxygen, pH, and other factors over daily and seasonal time scales can be difficult to replicate in lab settings. As a result, experimental animal physiology has often used mean values and static conditions to research organismal processes. While informative for basic science, this approach is likely a severe over simplification of what is occuring in nature. In order to ensure lab-based approaches are meaningful to real-world scenarios, researchers need to consider the mangnitude and regularity of environmental fluctuations, as well as the presense of co-stressors. Here, I'll showcase some recent data illustrating examples where variability was and was not incorporated into experimental design effectively, as well as discuss technological advancements that can assist in bringing the real environment into the lab.

Incorporating Variability into Physiological Experiments

The current rates of crop-yield increase are insufficient to meet the global food demands anticipated by 2050. While crop breeding has been one of the main pillars for securing yield progress in past decades, breeding programs are being confronted with new challenges due to the changing climate, particularly in areas where declining precipitation and increasing temperatures are more evident. Therefore, maximizing crop-yield potential and fortifying genetic resilience against abiotic and biotic stresses are critical to food security. High-throughput crop phenotyping is perceived as a key factor to accelerate crop genetic advance. Phenotyping not only facilitates conventional breeding, but it is necessary to fully exploit the capabilities of molecular breeding, and it can be exploited to predict breeding targets for the years ahead at the regional level through more advanced simulation models and decision support systems. In terms of phenotyping, it is necessary to determined which selection traits are relevant in each situation, and which phenotyping tools/ methods are the most suitable to assess such traits. Remote sensing methodologies are currently the most popular approaches, even when lab-based analyses are still relevant in many circumstances. On top of that, data processing and automation, together with machine learning/deep learning are contributing to a wide range of applications for phenotyping. This presentation will put emphasis on the most popular phenotyping approaches, including examples of phenotyping implementation for different traits and target environments.

Collaboration and Training for the Future of Advanced Therapies: The Cell and Gene Therapy Catapult

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Cis-regulated claudin 10c expression in gill is associated with variation in hypersaline seawater tolerance among species of killifish (Fundulus spp.)

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Collaboration and Training for the Future of Advanced Therapies: The Cell and Gene Therapy Catapult

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Next from SEB Conference Prague 2024

Cis-regulated claudin 10c expression in gill is associated with variation in hypersaline seawater tolerance among species of killifish (Fundulus spp.)

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES

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