Strukturelle Grundlagen für die Regulation von insulin-like growth factors (IGFs) durch IGF binding proteins (IGFBPs)

Insulin-like growth factor binding proteins (IGFBPs) control bioavailability, activity and distribution of IGF-I and –II in the serum. The study reported in this thesis employed techniques of nuclear magnetic resonance and X-ray crystallography to gain a more detailed understanding of the IGFBPs domain organization and structural requirements for binding to IGFs. This thesis presents structures of binary complexes between IGF-I and two amino-terminal domain constructs of IGFBP-4 and a model of the ternary complex of IGF-I, NBP-4 and the carboxyl-terminal domain.IGFBPs (Insulin-like growth factor binding proteins) kontrollieren die Bioverfügbarkeit, Aktivität und Verteilung von IGF-I und -II im Serum. Diese Doktorarbeit zeigt Strukturen des binären Komplexes zwischen IGF-I und zwei Konstrukten der amino-terminalen Domäne von IGFBP-4 (NBP-4) und ein Modell des ternären Komplexes von IGF-I, NBP-4 und der carboxy-terminalen Domäne (CBP-4). Ein neuer Einblick in die Beteiligung der N-terminalen Domäne von IGFBP an der Hemmung der IGF-IR Aktivität wurde durch NMR und ITC Experimente gewonnen. Das Model des ternären Komplexes erklärt das relative Arrangement der Domänen und IGF und zeigt, dass die C-terminale Domäne, CBP-4, sowohl die N-terminale Domäne als auch IGF-I berührt

Biomechanical Origins of Proprioceptor Feature Selectivity and Topographic Maps in the Drosophila Leg

Our ability to sense and move our bodies relies on proprioceptors, sensory neurons that detect mechanical forces within the body. Different subtypes of proprioceptors detect different kinematic features, such as joint position, movement, and vibration, but the mechanisms that underlie proprioceptor feature selectivity remain poorly understood. Using single-nucleus RNA sequencing (RNA-seq), we found that proprioceptor subtypes in the Drosophila leg lack differential expression of mechanosensitive ion channels. However, anatomical reconstruction of the proprioceptors and connected tendons revealed major biomechanical differences between subtypes. We built a model of the proprioceptors and tendons that identified a biomechanical mechanism for joint angle selectivity and predicted the existence of a topographic map of joint angle, which we confirmed using calcium imaging. Our findings suggest that biomechanical specialization is a key determinant of proprioceptor feature selectivity in Drosophila. More broadly, the discovery of proprioceptive maps reveals common organizational principles between proprioception and other topographically organized sensory systems

The genome of the crustacean Parhyale hawaiensis, a model for animal development, regeneration, immunity and lignocellulose digestion

The amphipod crustacean Parhyale hawaiensis is a blossoming model system for studies of developmental mechanisms and more recently regeneration. We have sequenced the genome allowing annotation of all key signaling pathways, transcription factors, and non-coding RNAs that will enhance ongoing functional studies. Parhyale is a member of the Malacostraca clade, which includes crustacean food crop species. We analysed the immunity related genes of Parhyale as an important comparative system for these species, where immunity related aquaculture problems have increased as farming has intensified. We also find that Parhyale and other species within Multicrustacea contain the enzyme sets necessary to perform lignocellulose digestion (“wood eating”), suggesting this ability may predate the diversification of this lineage. Our data provide an essential resource for further development of Parhyale as an experimental model. The first malacostracan genome will underpin ongoing comparative work in food crop species and research investigating lignocellulose as an energy source

Three dimensional reconstruction of energy stores for jumping in planthoppers and froghoppers from confocal laser scanning microscopy.

Jumping in planthopper and froghopper insects is propelled by a catapult-like mechanism requiring mechanical storage of energy and its quick release to accelerate the hind legs rapidly. To understand the functional biomechanics involved in these challenging movements, the internal skeleton, tendons and muscles involved were reconstructed in 3-D from confocal scans in unprecedented detail. Energy to power jumping was generated by slow contractions of hind leg depressor muscles and then stored by bending specialised elements of the thoracic skeleton that are composites of the rubbery protein resilin sandwiched between layers of harder cuticle with air-filled tunnels reducing mass. The images showed that the lever arm of the power-producing muscle changed in magnitude during jumping, but at all joint angles would cause depression, suggesting a mechanism by which the stored energy is released. This methodological approach illuminates how miniaturized components interact and function in complex and rapid movements of small animals

Data for: Machine learning reveals the control mechanics of the insect wing hinge.

Insects constitute the most species-rich radiation of metazoa, a success due to the evolution of active flight. Unlike pterosaurs, birds, and bats, the wings of insects did not evolve from legs, but are novel structures attached to the body via a biomechanically complex hinge that transforms tiny, high-frequency oscillations of specialized power muscles into the sweeping back-and-forth motion of the wings. The hinge consists of a system of tiny, hardened structures called sclerites that are interconnected to one another via flexible joints and regulated by the activity of specialized control muscles. Here, we imaged the activity of these muscles in a fly using a genetically encoded calcium indicator, while simultaneously tracking the 3D motion of the wings with high-speed cameras. Using machine learning approaches, we created a convolutional neural network that accurately predicts wing motion from the activity of the steering muscles, and an encoder-decoder that predicts the role of the individual sclerites on wing motion. By replaying patterns of wing motion on a dynamically scaled robotic fly, we quantified the effects of steering muscle activity on aerodynamic forces. A physics-based simulation that incorporates our model of the hinge generates flight maneuvers that are remarkably similar to those of free flying flies. This integrative, multi-disciplinary approach reveals the mechanical control logic of the insect wing hinge, arguably among the most sophisticated and evolutionarily important skeletal structures in the natural world