Article
Chemistry, Multidisciplinary
Johannes Morstein, Giovanna Romano, Belinda E. Hetzler, Ambrose Plante, Caleb Haake, Joshua Levitz, Dirk Trauner
Summary: This study develops tools for optical control of serotonin receptors, providing a new method for studying receptor function. By constructing a repeatable and reversible optical control system, this study lays the foundation for extending photopharmacology to the serotonin receptor family.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Alexander Sailer, Joyce C. M. Meiring, Constanze Heise, Linda N. Pettersson, Anna Akhmanova, Julia Thorn-Seshold, Oliver Thorn-Seshold
Summary: This study demonstrates the first cellular application of a near-quantitative photoswitch, allowing precise control over microtubule dynamics, cell cycle progression, and cell death in live cells. It shows the utility of hemithioindigo as a valuable scaffold for photocontrol of various biological targets, opening up new possibilities for high-precision microtubule research.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Chemistry, Medicinal
Sofia N. Sarabando, Andreia Palmeira, Maria Emilia Sousa, Maria Amparo F. Faustino, Carlos J. P. Monteiro
Summary: Photopharmacology is a promising alternative to traditional chemotherapy. This article discusses various photoswitches and photocleavage compounds, as well as their biological applications. It also mentions PROTACs containing azobenzene moieties and photocaged PROTACs. Porphyrins are highlighted as successful photoactive compounds in clinical contexts, such as photodynamic therapy and antimicrobial resistance prevention. The combination of photoswitches and photocleavage systems in porphyrins demonstrates the potential of photopharmacology and photodynamic action. Furthermore, porphyrins with antibacterial activity are described, utilizing the synergistic effect of photodynamic treatment and antibiotic therapy to combat bacterial resistance.
Article
Chemistry, Medicinal
Yongjin Xu, Chunxia Gao, Mans Andreasson, Liliana Haversen, Marta P. Carrasco, Cassandra Fleming, Thomas Lundback, Joakim Andreasson, Morten Grotli
Summary: In this study, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, allowing for photonic control of RET activity. By modifying the molecular structure, the difference in bioactivity between the two isomers was increased. The quinoline-based compound showed the most promising results, exhibiting significant bioactivity difference in both biochemical and cellular assays.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Li Gao, Joyce C. M. Meiring, Constanze Heise, Ankit Rai, Adrian Mueller-Deku, Anna Akhmanova, Julia Thorn-Seshold, Oliver Thorn-Seshold
Summary: Optical methods to modulate microtubule dynamics have the potential to decrypt the roles of the cytoskeleton in biology with high resolution. However, the development of optical microtubule stabilisers is still limited. In this study, we introduce STEpos as GFP-orthogonal, light-responsive microtubule stabilisers, which significantly improve potency, solubility, and ease-of-use compared to previous stabilisers. These reagents can greatly contribute to high-precision research in cytoskeleton biophysics, cargo transport, cell motility, cell division, development, and neuroscience.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
John T. Kalyvas, Paula Facal Marina, Damian L. Stachura, John R. Horsley, Andrew D. Abell
Summary: A novel strategy using UV light to activate and deliver an antimicrobial therapeutic agent for treating Staphylococcus aureus (S. aureus) skin infections is introduced. The active peptide, derived from a photoswitchable gramicidin S analogue immobilized on a wearable patch, exhibits antimicrobial activity against S. aureus without harming red blood cells. The antimicrobial properties of the peptide can be switched off within seconds by irradiation with visible light, providing an ideal approach to regulate antibiotic activity and potentially mitigate resistance.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Pharmacology & Pharmacy
Sergei Nikonov, Natalia Dolgova, Raghavi Sudharsan, Ivan Tochitsky, Simone Iwabe, Jose-Manuel Guzman, Russell N. N. Van Gelder, Richard H. H. Kramer, Gustavo D. D. Aguirre, William A. A. Beltran
Summary: This study reports the effects of DENAQ, a second-generation azobenzene-based photoswitch, on retinal ganglion cells in canine retinas. DENAQ treatment increases light sensitivity in degenerated canine retinas and induces responses in previously non-responsive cells. However, limited solubility and ocular toxicity hinder the therapeutic potential of DENAQ.
Article
Biochemistry & Molecular Biology
F. Wages, P. Lentes, T. Griebenow, R. Herges, C. Peifer, E. Maser
Summary: Testosterone depletion is a common goal in treating hormone-dependent prostate cancer. This study investigates the inhibition of 17SHSD3 by a compound called diazocine and finds that irradiation does not significantly affect its inhibitory effect. However, a chemical modification of the diazocine is detected after light treatment, potentially rendering it ineffective.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Biochemistry & Molecular Biology
Susanna Eli, Rossella Castagna, Marina Mapelli, Emilio Parisini
Summary: Microtubules are essential components of the cytoskeleton and play critical roles in various cellular processes. They are potential targets for the treatment of diseases, including cancer. This article summarizes recent experimental and computational approaches for identifying microtubule modulators and delivery strategies.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Carlo Matera, Pablo Calve, Veronica Casado-Anguera, Rosalba Sortino, Alexandre M. J. Gomila, Estefania Moreno, Thomas Gener, Cristina Delgado-Sallent, Pau Nebot, Davide Costazza, Sara Conde-Berriozabal, Merce Masana, Jordi Hernando, Vicent Casado, M. Victoria Puig, Pau Gorostiza
Summary: Understanding the dopaminergic system is a priority, and dysregulation of dopamine receptors is associated with major neurological disorders. Current tools for studying the endogenous dopaminergic circuits are limited. This study introduces azodopa, a photoswitchable ligand that enables reversible control of dopaminergic transmission. Azodopa has shown efficacy in wild-type animals and has the potential for remote control of dopaminergic neurotransmission.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pharmacology & Pharmacy
Shin Mizukami
Summary: This article reviews the recent developments in technologies for the optical control of biomolecular functions. It focuses on two approaches: organic chemistry-based technology and protein science-based technology. The advantages and disadvantages of these two technologies are discussed based on the research strategies and results.
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN
(2022)
Article
Chemistry, Organic
Pascal Lentes, Jeremy Rudtke, Thomas Griebenow, Rainer Herges
Summary: Novel nitrogen-bridged diazocines with formyl or acetyl groups and halogen substituents were synthesized and showed promising photophysical properties in acetonitrile and water. The use of an oxidative approach increased the yields of intramolecular azo cyclizations. Water-soluble diazocines exhibited high photoconversion yields, making them potential candidates for applications in photopharmacology.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
C. Wang, Y. Liu
Summary: In this work, an all visible-light-regulated supramolecular photo-switch was constructed based on a pyridinium-modified diarylethene derivative and cucurbit[8]uril. The switch exhibited efficient photocyclization and strong thermally activated delayed fluorescence, which could be regulated by visible light. The research has potential applications in information encryption.
MATERIALS TODAY CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Daniel Offenbartl-Stiegert, Alexia Rottensteiner, Adam Dorey, Stefan Howorka
Summary: Controlling biological processes with light allows precise and selective activation in a non-invasive and non-toxic manner. Researchers have developed a synthetic light-gated nanostructure that controls membrane transport through a controllable lid, with potential applications in biotechnology, drug release, and synthetic cells.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Engineering, Environmental
Feng Zhang, Jiawei Qian, Weixu Dong, Yifan Qu, Jingwei Chen, Hao Wang, Li-Feng Chen
Summary: This study proposes a facile tip-shielding strategy to effectively suppress Zn dendrites and side reactions on Zn anodes. The optimized electrode assembly achieved significantly enhanced cycling performance at high current densities.
CHEMICAL ENGINEERING JOURNAL
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Florian Mentzel, Kevin Kroeninger, Michael Lerch, Olaf Nackenhorst, Jason Paino, Anatoly Rosenfeld, Ayu Saraswati, Ah Chung Tsoi, Jens Weingarten, Markus Hagenbuchner, Susanna Guatelli
Summary: In this study, a fast and accurate dose estimation method for novel treatments is proposed using digital phantoms and machine learning techniques. The generative adversarial network model is able to accurately simulate the MC simulation with small deviations and predict radiation dose with short computation time.
Article
Chemistry, Multidisciplinary
Linh T. Tran, David Bolst, Benjamin James, Vladimir Pan, James Vohradsky, Stefania Peracchi, Lachlan Chartier, Emily Debrot, Susana Guatelli, Marco Petasecca, Michael Lerch, Dale Prokopovich, Zeljko Pastuovic, Marco Povoli, Angela Kok, Taku Inaniwa, Sung Hyun Lee, Naruhiro Matsufuji, Anatoly B. Rosenfeld
Summary: The Centre for Medical Radiation Physics introduced the concept of Silicon On Insulator (SOI) microdosimeters with 3-Dimensional (3D) cylindrical sensitive volumes (SVs) mimicking the dimensions of cells in an array. Several designs of high-definition 3D SVs fabricated using 3D MEMS technology were implemented. The SVs were used to evaluate the relative biological effectiveness (RBE) of heavy ions and protons delivered by different particle therapy centers.
APPLIED SCIENCES-BASEL
(2022)
Article
Instruments & Instrumentation
Jeremy Davis, Andrew Dipuglia, Matthew Cameron, Jason Paino, Ashley Cullen, Susanna Guatelli, Marco Petasecca, Anatoly Rosenfeld, Michael Lerch
Summary: Ensuring sufficient quality assurance measures is crucial for the successful transition of synchrotron-based microbeam radiation therapy from animal studies to human trials. Transmission detectors of different thicknesses were used to monitor and quantify the impact on photon energy spectra and dose deposition. It was found that a 375 μm thick detector led to a 1-6% decrease in broad-beam and microbeam peak dose, while a 10 μm thick detector had negligible impact on photon energy spectra and dose delivery. Based on best practice, the authors recommend utilizing 10 mm thick transmission detectors as a real-time quality assurance and beam-monitoring tool during MRT.
JOURNAL OF SYNCHROTRON RADIATION
(2022)
Article
Engineering, Electrical & Electronic
V. A. Pan, L. T. Tran, Z. Pastuovic, D. Hill, J. Williams, A. Kok, M. Povoli, A. Pogossov, S. Peracchi, D. Boardman, J. Davis, S. Guatelli, M. Petasecca, M. L. F. Lerch, A. B. Rosenfeld
Summary: A new batch of microdosimeters was studied for their charge collection efficiency (CCE) and radiation hardness for various applications. The microdosimeters were characterized with different ion beams and a gamma source, and a negative pulse was observed in addition to the positive pulses generated by incident ions. It was determined that the negative pulse originated from the support wafer due to the displacement current phenomenon. Radiation hardness study showed a slight CCE deficit, but overall the microdosimeters were found suitable for space and medical applications.
IEEE TRANSACTIONS ON NUCLEAR SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Alka Rao, Niels A. W. de Kok, Arnold J. M. Driessen
Summary: Cellular membranes play essential roles in compartmentalization, permeability maintenance, and fluidity in all three domains of life. Archaea, as the third domain of life, have unique phospholipid compositions. The study focuses on Sulfolobus acidocaldarius, an archaeon with a membrane dominated by glycerol dialkyl glycerol tetraethers (GDGTs), and the effects of the antifungal terbinafine on its lipidome and transcriptome. The results show that terbinafine treatment leads to growth phase-dependent depletion of GDGTs and the accumulation of bilayer-forming dialkyl glycerol diethers (DGDs). Transcriptomic analysis reveals significant differential expression of genes involved in respiratory stress, isoprenoid biosynthesis, and saturation. Overall, terbinafine inhibition affects the respiratory complex, motility, cell envelope, fatty acid metabolism, and GDGT cyclization in S. acidocaldarius.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Matthew J. Large, Marco Bizzarri, Lucio Calcagnile, Mirco Caprai, Anna Paola Caricato, Roberto Catalano, Giuseppe A. P. Cirrone, Tommaso Croci, Giacomo Cuttone, Sylvain Dunand, Michele Fabi, Luca Frontini, Benedetta Gianfelici, Catia Grimani, Maria Ionica, Keida Kanxheri, Michael L. F. Lerch, Valentino Liberali, Maurizio Martino, Giuseppe Maruccio, Giovanni Mazza, Mauro Menichelli, Anna Grazia Monteduro, Francesco Moscatelli, Arianna Morozzi, Stefania Pallotta, Andrea Papi, Daniele Passeri, Maddalena Pedio, Giada Petringa, Francesca Peverini, Lorenzo Piccolo, Pisana Placidi, Gianluca Quarta, Silvia Rizzato, Alessandro Rossi, Giulia Rossi, Vincent de Rover, Federico Sabbatini, Leonello Servoli, Alberto Stabile, Cinzia Talamonti, Luca Tosti, Mattia Villani, Richard J. Wheadon, Nicolas Wyrsch, Nicola Zema, Marco Petasecca
Summary: Microbeam radiation therapy (MRT) is a promising alternative radiotherapy treatment method that effectively controls radioresistant tumors while sparing healthy tissue. In this study, radiation-hardened a-Si:H diodes were characterized for x-ray dosimetry and real-time beam monitoring in high-flux beamlines for MRT. The devices showed excellent radiation hardness and accurate dosimetric performance, making them suitable for high dose-rate environments like FLASH and MRT.
PHYSICS IN MEDICINE AND BIOLOGY
(2023)
Article
Oncology
Felix Jaekel, Jason Paino, Elette Engels, Mitzi Klein, Micah Barnes, Daniel Hausermann, Christopher Hall, Gang Zheng, Hongxin Wang, Guido Hildebrandt, Michael Lerch, Elisabeth Schueltke
Summary: Microbeam radiotherapy (MRT) is a high dose rate radiotherapy technique that has shown high therapeutic efficacy in different tumor entities, including lung cancer. A toxicity study was conducted on the spinal cord during irradiation of a target in the thoracic cavity. Neurologic signs occurred after irradiation with MRT peak doses of 450-800 Gy.
Article
Oncology
Florian Mentzel, Jason Paino, Micah Barnes, Matthew Cameron, Stephanie Corde, Elette Engels, Kevin Kroeninger, Michael Lerch, Olaf Nackenhorst, Anatoly Rosenfeld, Moeava Tehei, Ah Chung Tsoi, Sarah Vogel, Jens Weingarten, Markus Hagenbuchner, Susanna Guatelli
Summary: This study developed a fast and accurate machine learning (ML) dose engine for Microbeam Radiation Therapy (MRT) in rat patients. The ML model was trained with Monte Carlo (MC) simulations and showed satisfactory dose description and fast dose mapping capabilities.
Article
Engineering, Multidisciplinary
Thomas Breslin, Jason Paino, Marie Wegner, Elette Engels, Stefan Fiedler, Helen Forrester, Hannes Rennau, John Bustillo, Matthew Cameron, Daniel Hausermann, Christopher Hall, Dieter Krause, Guido Hildebrandt, Michael Lerch, Elisabeth Schueltke
Summary: The production of anthropomorphic phantoms from tissue-equivalent materials is challenging yet necessary for clinical trials in radiotherapy. In this study, we designed and produced a partial upper arm phantom and compared it to patient data. Dose simulations and experiments were conducted to validate the phantom's accuracy. The results demonstrated the effectiveness of the phantom in experimental high-dose-rate radiotherapy.
Article
Materials Science, Multidisciplinary
Rajib Chandra Das, Marcela L. Chaki, Ronald Sluyter, Michael Lerch, Konstantin Konstantinov
Summary: This study examined the ROS scavenging activity of Y2O3 nanomaterials with 2D-like morphology in a UV radiation environment and in the Fenton system. The materials were synthesized using a chemical precipitation method and annealed under different gas environments. The Y2O3 nanoparticles showed promising potential in preventing dye degradation and ROS damage caused by radiation.
Article
Radiology, Nuclear Medicine & Medical Imaging
Micah J. Barnes, Nader Afshar, Matthew Cameron, Daniel Hausermann, Nicholas Hardcastle, Michael Lerch
Summary: Researchers have developed a novel collimator design for synchrotron radiotherapy applications on the Imaging and Medical Beamline (IMBL) at the ANSTO Australian Synchrotron. The collimator enables dynamically delivered conformal treatment fields and has been successfully demonstrated. It is ready to support forthcoming canine treatments on IMBL.
Article
Nuclear Science & Technology
Ilia Filipev, Giordano Biasi, Joel Poder, Michael Lerch, Marco Petasecca, Susanna Guatelli, Tomas Kron, Anatoly Rosenfeld
Summary: In this study, a Monte Carlo simulation model was developed to investigate how the components of a detector assembly based on a 2D silicon array sensor contribute to the observed angular dependence. The presence of silicon had the largest effect on energy deposition, while the thickness of the air gap had a significant impact on the variation in angular dependence between different field sizes. Other component dimensions and the presence of the PCB layer did not show significant influence on the angular response. Further development of the detector assembly's design should focus on mechanical robustness and optimizing the air gap dimensions.
RADIATION MEASUREMENTS
(2023)
Article
Multidisciplinary Sciences
Adela Melcrova, Sourav Maity, Josef Melcr, Niels A. W. de Kok, Mariella Gabler, Jonne van der Eyden, Wenche Stensen, John S. M. Svendsen, Arnold J. M. Driessen, Siewert J. Marrink, Wouter H. Roos
Summary: This study investigates the mechanism of action of the antimicrobial cationic tripeptide AMC-109. It was found that AMC-109 self-assembles into stable aggregates with a cationic surface, and then inserts into the bacterial membrane disrupting membrane nanodomains, thus affecting membrane function without forming pores. The results suggest that AMC-109 is a peptide with enhanced selectivity for bacterial membranes.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Shucong Li, Michael Aizenberg, Michael Lerch, Joanna Aizenberg
Summary: Synthetic structures that can undergo controlled movement are essential for developing new technologies in robotics, healthcare, and sustainable materials. However, programming motion at the microscale is challenging. Therefore, new approaches that combine top-down and bottom-up methods at the microscale are urgently needed to achieve motional complexity.
ACCOUNTS OF MATERIALS RESEARCH
(2023)
Meeting Abstract
Radiology, Nuclear Medicine & Medical Imaging
F. Mentzel, M. Barnes, K. Krninger, M. Lerch, O. Nackenhorst, J. Paino, A. Rozenfeld, A. Tsoi, J. Weingarten, M. Hagenbuchner, S. Guatelli
