Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.78M | Year: 2013
Organic Bioelectonics is a new discipline which holds promise to shape, direct, and change future medical treatments in a revolutionary manner over the next decades. At the moment Europe has a unique leading position in this area, being almost all the world-leading groups in this field located in Europe and constituting the core of this international training network. However, realizing the promise of Organic bioelectronics requires research and training not only crossing disciplines, such as electrical engineering, biology, chemistry, physics, and materials science, but also crossing our European countries. The EU will add value on the global scene only if it acts jointly. OrgBIO is at the core of European technological innovation and will become an indispensable part of the educational canon. It will establish a world-class training platform spreading around the highly interdisciplinary / intersectorial European-led area of organic bioelectronics. Education along with science and entrepreneurial mindsets and attitudes is the core of the OrgBIO training programme, which aims at excellence and innovation, at all level. Excellence in science is guaranteed by the world-leading groups which founded this research area. Innovation in education is guaranteed by the involvement of researchers on education, business experts. Using different sensors, actuators, electronic and interconnect technologies the network will develop multifunctional systems based on organic devices and materials with high sensitivity that are also flexible, conformable and present over large areas for various biomedical / biological applications in the life science. Multi-analyte and disposable analytical systems manufactured by large-area printing methods will provide services to the individuals and healthcare community. Targeted implemented interactions with a wide network of venture capitals and business actors will immediately transfer the research outcome to the European Industry.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.90M | Year: 2015
Anaemia is the most common pathological condition affecting 1.6 billion individuals worldwide. It thus presents a serious health care problem and an economic burden. Reduction in red blood cell (RBC) number can be caused by blood loss, diet, stress conditions including endurance sport, and pathologies which are caused by primary genetic aberrations or are secondary to the malfunction of other cell types. Transfusion of RBC, which is often the only cure for severe cases of anaemia, is associated with risks such as thrombosis and transfusion reactions due to allo-immunisation. There is an unmet need to improve treatment of anaemia through early and accurate diagnosis, targeted treatment, and increased safety and effectiveness of RBC transfusion. The aim of RELEVANCE is to improve fast and cost-effective diagnosis of the underlying cause of primary anaemia, and to improve treatment options for both general and personalised medicine. We defined five key objectives: (1) to improve diagnostics of anaemia, particularly for hereditary rare forms of anaemia (RA); (2) to find novel treatments for anaemia that target RBC production, ageing and clearance; (3) to reduce premature loss of RBC following transfusion; (4) to produce cultured RBC for transfusion; (5) to monitor and optimise RBC function during sport and exercise. RELEVANCE will train 15 early stage researchers (ESR) at four SMEs and eight academic partners, two of whom are at blood supply centres and two are diagnostic centres for RA. The continuous interactions between the clinic, blood supply centers, basic research, and industry will select for the most relevant unmet medical needs, and will stimulate innovative procedures that are immediately probed for applicability and validity both in a research and a clinical setting. RELEVANCE will organize three open access summer schools, extending training beyond the ESR of the ITN sustaining the critical number of young talented professionals in the field.
Seifert A.,Nanion Technologies GmbH |
Gopfrich K.,University of Cambridge |
Burns J.R.,University College London |
Fertig N.,Nanion Technologies GmbH |
And 2 more authors.
ACS Nano | Year: 2015
Membrane-spanning nanopores from folded DNA are a recent example of biomimetic man-made nanostructures that can open up applications in biosensing, drug delivery, and nanofluidics. In this report, we generate a DNA nanopore based on the archetypal six-helix-bundle architecture and systematically characterize it via single-channel current recordings to address several fundamental scientific questions in this emerging field. We establish that the DNA pores exhibit two voltage-dependent conductance states. Low transmembrane voltages favor a stable high-conductance level, which corresponds to an unobstructed DNA pore. The expected inner width of the open channel is confirmed by measuring the conductance change as a function of poly(ethylene glycol) (PEG) size, whereby smaller PEGs are assumed to enter the pore. PEG sizing also clarifies that the main ion-conducting path runs through the membrane-spanning channel lumen as opposed to any proposed gap between the outer pore wall and the lipid bilayer. At higher voltages, the channel shows a main low-conductance state probably caused by electric-field-induced changes of the DNA pore in its conformation or orientation. This voltage-dependent switching between the open and closed states is observed with planar lipid bilayers as well as bilayers mounted on glass nanopipettes. These findings settle a discrepancy between two previously published conductances. By systematically exploring a large space of parameters and answering key questions, our report supports the development of DNA nanopores for nanobiotechnology. © 2014 American Chemical Society.
Grimm C.,Ludwig Maximilians University of Munich |
Barthmes M.,Nanion Technologies GmbH |
Wahl-Schott C.,Ludwig Maximilians University of Munich
Handbook of Experimental Pharmacology | Year: 2014
TRPML3 belongs to the MCOLN (TRPML) subfamily of transient receptor potential (TRP) channels comprising three genes in mammals. Since the discovery of the pain sensing, capsaicin- and heat-activated vanilloid receptor (TRPV1), TRP channels have been found to be involved in regulating almost all kinds of our sensory modalities. Thus, TRP channel members are sensitive to heat or cold; they are involved in pain or osmosensation, vision, hearing, or taste sensation. Loss or mutation of TRPML1 can cause retina degeneration and eventually blindness in mice and men (mucolipidosis type IV). Gain-of-function mutations in TRPML3 cause deafness and circling behavior in mice. A special feature of TRPML channels is their intracellular expression. They mostly reside in membranes of organelles of the endolysosomal system such as early and late endosomes, recycling endosomes, lysosomes, or lysosome-related organelles. Although the physiological roles of TRPML channels within the endolysosomal system are far from being fully understood, it is speculated that they are involved in the regulation of endolysosomal pH, fusion/fission processes, trafficking, autophagy, and/or (hormone) secretion and exocytosis. © Springer-Verlag Berlin Heidelberg 2014.
Stoelzle-Feix S.,Nanion Technologies GmbH
Methods in Molecular Biology | Year: 2014
A successful robotic approach of the patch clamp technique is based on planar patch clamp chips where a glass pipette, as used in conventional patch clamping, is replaced by a thin planar glass sheet with a small hole in the middle. Automated patch clamp (APC) systems utilizing this chip design offer higher throughput capabilities and ease of use and thus have become common in basic research, drug development, and safety screening. Further development of existing devices and introduction of new systems widen the range of possible experiments and increase throughput. Here, two features with different areas of applications that meet the needs of drug discovery researchers and basic researchers alike are described. The utilized system is a medium throughput APC device capable of recording up to eight cells simultaneously. The temperature control capability and the possibility to perform recordings not only in the voltage clamp but also in the current clamp mode are described in detail. Since eight recordings can be generated in parallel without compromising data quality, reliable and cost-effective and time-effective screening of compounds against ion channels using voltage clamp and current clamp electrophysiology can be performed. © 2014 Springer Science+Business Media New York.
Moparthi L.,Lund University |
Survery S.,Lund University |
Kreir M.,Nanion Technologies GmbH |
Kreir M.,Jacobs University Bremen |
And 5 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014
We have purified and reconstituted human transient receptor potential (TRP) subtype A1 (hTRPA1) into lipid bilayers and recorded single-channel currents to understand its inherent thermo- and chemosensory properties as well as the role of the ankyrin repeat domain (ARD) of the N terminus in channel behavior. We report that hTRPA1 with and without its N-terminal ARD (Δ1-688 hTRPA1) is intrinsically cold-sensitive, and thus, cold-sensing properties of hTRPA1 reside outside the N-terminal ARD. We show activation of hTRPA1 by the thiol oxidant 2-((biotinoyl)amino)ethyl methanethiosulfonate (MTSEA-biotin) and that electrophilic compounds activate hTRPA1 in the presence and absence of the N-terminal ARD. The nonelectrophilic compounds menthol and the cannabinoid Δ9- tetrahydrocannabiorcol (C16) directly activate hTRPA1 at different sites independent of the N-terminal ARD. The TRPA1 antagonist HC030031 inhibited cold and chemical activation of hTRPA1 and Δ1-688 hTRPA1, supporting a direct interaction with hTRPA1 outside the N-terminal ARD. These findings show that hTRPA1 is an intrinsically cold- and chemosensitive ion channel. Thus, second messengers, including Ca2+, or accessory proteins are not needed for hTRPA1 responses to cold or chemical activators. We suggest that conformational changes outside the N-terminal ARD by cold, electrophiles, and nonelectrophiles are important in hTRPA1 channel gating and that targeting chemical interaction sites outside the N-terminal ARD provides possibilities to fine tune TRPA1-based drug therapies (e.g., for treatment of pain associated with cold hypersensitivity and cardiovascular disease).
Burns J.R.,University College London |
Seifert A.,Nanion Technologies GmbH |
Fertig N.,Nanion Technologies GmbH |
Howorka S.,University College London
Nature Nanotechnology | Year: 2016
Biological ion channels are molecular gatekeepers that control transport across cell membranes. Recreating the functional principle of such systems and extending it beyond physiological ionic cargo is both scientifically exciting and technologically relevant to sensing or drug release. However, fabricating synthetic channels with a predictable structure remains a significant challenge. Here, we use DNA as a building material to create an atomistically determined molecular valve that can control when and which cargo is transported across a bilayer. The valve, which is made from seven concatenated DNA strands, can bind a specific ligand and, in response, undergo a nanomechanical change to open up the membrane-spanning channel. It is also able to distinguish with high selectivity the transport of small organic molecules that differ by the presence of a positively or negatively charged group. The DNA device could be used for controlled drug release and the building of synthetic cell-like or logic ionic networks. © 2016 Macmillan Publishers Limited.
Agency: European Commission | Branch: FP7 | Program: MC-ERG | Phase: PEOPLE-2007-2-2.ERG | Award Amount: 45.00K | Year: 2009
The gold standard for obtaining data on ion channel function is the patch clamp method. The patch clamp technique is very labor intensive and has ultra low data throughput which has been highly motivating for the development of automated patch clamp systems. Nanion has developed a technology for performing automated patch clamp recordings on planar glass substrates, with comparable recording quality as with conventional patch clamping, however, lacking the possibility to very briefly expose the cells to different solutions. If exposure times are too long, this can have adverse effects when investigating ion channels that activate on the addition of agonists (ligand gated ion channels). Ligand gated ion channels are gaining more attention in research and drug development because of their involvement in disease. These ion channels often display desensitization, resulting in a diminishing compound response, during constant stimulation. Recovery kinetics often depends on exposure time, thus are brief exposure times desirable. We aim at developing a method for very short compound exposure using automated patch clamp by combining microfluidic structures for liquid administration to the patch clamp substrate. A robotic pipettor arm applies all solutions to the microchannels and by subsequently aspirating two differnt solutions of buffer into the pipette, and immediately adding this stack of solutions to the cell, the cell experiences a very brief exposure of agonist, directly followed by wash buffer. This way, exposure times are anticipated to be shorter than 1 second, with switching times in the order of 50 ms. This would allow for accurate experiments on ligand gated ion channels that exhibit rapid desensitization , which in turn would be useful in ion channel research on channelopathies, and to facilitate the drug development of compounds modulating ligand gated ion channels.
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.30M | Year: 2013
Multidrug resistant bacteria are now ubiquitous in both hospitals and the larger community. Drug-resistant pathogens are becoming increasingly pervasive, for example, the resurrection of tuberculosis provides one ominous example highlighting the risk associated with evolved drug resistance. Moreover, many pharmaceutical companies abandoned this field and no truly novel active antibacterial compounds are currently in clinical trials. Obviously we need new antibacterial molecules and maybe, novel strategies to develop antibiotics. The novel aspect here is to use state-in-the art techniques to quantify rate limiting steps of individual components involved antibiotic penetration and to validate them at the cellular level. Such a system biology approach identifies bottlenecks of existing antibiotics and might suggest novel antibiotic therapy. In Gram-negative bacteria, where influx and efflux systems located in the Outer Membrane represent a physical bottleneck for any antibiotic to reach a potential target. The aim is to investigate the molecular and cellular mechanisms at the basis of the influx and efflux processes and to teach scientists with different scientific background to go beyond the classical faculty boarder. Bringing nanotechnology, physics, chemistry, computer modeling, pharmacology, microbiology together will facilitate the transfer of expertise acquired within the network in both academic and industry. To achieve these goals we propose a training program allowing young researcher to collaborate across traditional faculty boarder. Three partners from the private sector will actively participate, the first one is a SME developing unique nanodevices allowing high-throughput drug screening in the field of electrophysiology, the second one is engaged in developing novel antibiotics and the third one is working on drug screening and characterization. Moreover three global pharmaceutical companies will accept students for secondments.
Steller L.,Leibniz Institute for Solid State and Materials Research |
Kreir M.,Nanion Technologies GmbH |
Salzer R.,TU Dresden
Analytical and Bioanalytical Chemistry | Year: 2012
The single-molecule selectivity and specificity of the binding process together with the expected intrinsic gain factor obtained when utilizing flow through a channel have attracted the attention of analytical chemists for two decades. Sensitive and selective ion channel biosensors for high-throughput screening are having an increasing impact on modern medical care, drug screening, environmental monitoring, food safety, and biowarefare control. Even virus antigens can be detected by ion channel biosensors. The study of ion channels and other transmembrane proteins is expected to lead to the development of new medications and therapies for a wide range of illnesses. From the first attempts to use membrane proteins as the receptive part of a sensor, ion channels have been engineered as chemical sensors. Several other types of peptidic or nonpeptidic channels have been investigated. Various gating mechanisms have been implemented in their pores. Three technical problems had to be solved to achieve practical biosensors based on ion channels: the fabrication of stable lipid bilayer membranes, the incorporation of a receptor into such a structure, and the marriage of the modified membrane to a transducer. The current status of these three areas of research, together with typical applications of ion-channel biosensors, are discussed in this review. © 2011 Springer-Verlag.