Review
Biochemistry & Molecular Biology
Elnaz Aledavood, Beatrice Selmi, Carolina Estarellas, Matteo Masetti, F. Javier Luque
Summary: This review focuses on therapeutic treatments for influenza, specifically targeting key viral proteins including the M2 proton channel and neuraminidase. The article highlights the efforts in studying the M2 proton channel and discusses the challenges in developing efficient small molecule inhibitors and dealing with resistant strains.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Microbiology
Fadi G. Alnaji, William K. Reiser, Joel Rivera-Cardona, Aartjan J. W. te Velthuis, Christopher B. Brooke
Summary: Deletion-containing viral genomes (DelVGs) are commonly produced during influenza A virus infection, influenced by specific molecular mechanisms such as direct sequence repeats and base enrichment. DelVGs face a significant bottleneck during genome packaging, with larger DelVGs showing signs of enrichment in packaged virions, suggesting size as an important determinant of packaging efficiency.
Article
Nanoscience & Nanotechnology
Haonan Qu, Shaoming Dai, Yanquan Qu, Siyun Zhang, Mingxiang Lu, Zhiyan Lu, Juan Zhou, Haibing Li
Summary: The study constructed a sub-nanoporous proton transport membrane with good selectivity and high transport capacity for protons by exploiting the size effect of sub-nanometer pores. The membrane is meaningful for the construction of nanofluidic diodes and energy conversion applications.
ACS APPLIED NANO MATERIALS
(2022)
Article
Chemistry, Multidisciplinary
Anna K. Wright, Joana Paulino, Timothy A. Cross
Summary: This report investigates the structure of the S31N M2 protein from Influenza A virus in the presence of a high molar ratio of lipid. It shows that a high lipid to protein ratio stabilizes a 4-fold-symmetric conformation of the M2 membrane protein. The study highlights the importance of both the character and abundance of the emulated membrane environment for achieving the native protein structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Biophysics
Kelly L. McGuire, Phillip Smit, Daniel H. Ess, Jonathan T. Hill, Roger G. Harrison, David D. Busath
Summary: Copper complexes can block the influenza virus M2 proton channel, reduce cytotoxicity, and zebrafish-embryo toxicity, by forming coordination complexes with histidine in the proton channel. The energetics of binding and rate constants suggest a two-step process, with copper complex binding as the first step and formation of a Cu-histidine coordination complex as the slow step in current blockage. Electrophysiology and DFT studies also demonstrate that the complexes are effective in blocking the G34E amantadine-resistant mutant.
BIOPHYSICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Phuong Thi Hoang, Quynh Xuan Thi Luong, Seungchan Cho, Yongjun Lee, Kyungho Na, Ramadhani Qurrota Ayun, Thuy Thi Bich Vo, Taehyun Kim, Sukchan Lee
Summary: This study discovered a single-chain variable fragment (scFv) targeting the M2 protein of influenza A H1N1/PR8, which showed neutralizing activity through plaque inhibition in virus replication. The scFv and single-domain V-L proteins were obtained, and a bivalent anti-M2 single-domain V-L antibody was engineered to improve antigen binding. Both mono- and bivalent antibodies exhibited neutralizing activity against influenza virus A.
Article
Microbiology
Haiying Mao, Lei Cao, Ting Xu, Xiaohan Xia, Peilei Ren, Pengfei Han, Chengfei Li, Xianfeng Hui, Xian Lin, Kun Huang, Meilin Jin
Summary: This study identified a novel host factor, YWHAG, that interacts with the IAV matrix protein M2 and regulates viral budding. Knockout of YWHAG increased viral production, while overexpression reduced the titer of virus progeny.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiaoman Liu, Fengwen Xu, Lili Ren, Fei Zhao, Yu Huang, Liang Wei, Yingying Wang, Conghui Wang, Zhangling Fan, Shan Mei, Jingdong Song, Zhendong Zhao, Shan Cen, Chen Liang, Jianwei Wang, Fei Guo
Summary: MARCH8 acts as an important player in the host anti-influenza virus defense by targeting M2 protein and inhibiting viral replication. The discovery that H1N1 influenza A virus has evolved to resist MARCH8-mediated ubiquitination and degradation sheds light on the inhibitory effects of MARCH8 on virus transmission within the human population.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ravi K. Gupta, Petra Mlcochova
Summary: SARS-CoV-2 infection triggers redistribution of cyclin D1 and D3 from the nucleus to the cytoplasm, followed by proteasomal degradation. Cyclin D3 interacts with SARS-CoV-2 proteins and affects the assembly and release of newly produced virions, highlighting the importance of understanding the virus-host interactions.
Article
Chemistry, Medicinal
Dimitrios Kolokouris, Iris E. Kalenderoglou, Antonios Kolocouris
Summary: Molecular dynamics simulations have accurately described the structure and interactions of the influenza A M2 protein in the membrane environment, providing valuable insights for viroporin systems and potential drug targets.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Chemistry, Multidisciplinary
Kumar Tekwani Movellan, Riza Dervisoglu, Stefan Becker, Loren B. Andreas
Summary: The study reveals the presence of a bound water molecule forming a hydrogen bond with the δ1 nitrogen of histidine 37 in the M2 conductance domain.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Chuandi Yu, Wen Ding, Lei Zhu, Yuhang Zhou, Yingkui Dong, Ling Li, Juanjuan Liu, Yizhuo Wang, Zehua Li, Lina Zhu, FaJun Chen, Maosen Ruan, Dongming Qian, Yujuan Wang, Bo Wu, Huangtao Xu, Ming Li, Yunchen Bi, Hao Wang, Weiqian Wang, Peng Chao, Lei Xing, Bing Shen, Han Dai, Lisha Zha, Hongxin Zhao, Junfeng Wang
Summary: By incorporating M2(1-46) protein into nanodiscs, researchers generated vNARs that specifically bind to tetrameric M2 proteins and can block ion influx through M2 channels. This study provides a new approach for developing influenza vaccines by targeting the M2 protein.
Article
Chemistry, Multidisciplinary
Ronja Rabea Paschke, Swantje Mohr, Sascha Lange, Adam Lange, Jacek Kozuch
Summary: Viroporins are small viral ion channels that play essential roles during viral infections. Using surface-enhanced infrared absorption spectroscopy, we track and quantify the large-scale structural changes during opening of the Influenza A viroporin, the M2 proton channel, in a model membrane. This motion is blocked by inhibition providing a clear spectroscopic strategy to explore mechanisms of viroporin function and test new antiviral drugs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jinmei Yang, Yuxian Lu, Lei Jin, Chunxiao Zhao, Yuang Chen, Yang Xu, Fanfan Chen, Jiandong Feng
Summary: This study optically visualized proton transport pathways through nanopores and hydrophilic interfaces using fluorescence signals, revealing an increase in fluorescence intensity at negative voltage due to lateral transport. With the temporal resolution of optical imaging, the technique enabled a comprehensive analysis of proton transport dynamics.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Marianna Stampolaki, Anja Hoffmann, Kumar Tekwani, Kyriakos Georgiou, Christina Tzitzoglaki, Chunlong Ma, Stefan Becker, Patrick Schmerer, Kristin Doering, Ioannis Stylianakis, Andreea L. Turcu, Jun Wang, Santiago Vazquez, Loren B. Andreas, Michaela Schmidtke, Antonios Kolocouris
Summary: In this study, we compared the antiviral activities of 57 adamantyl amines against influenza A virus. Four compounds showed high potency against the wild-type M2 virus, while 27 compounds exhibited moderate to low activity. Several compounds also showed activity against the amantadine-resistant L26F M2 virus, but only three of them blocked the L26F M2-mediated proton current. Moreover, one compound was found to be a triple blocker of WT, L26F, and V27A M2 channels, but it did not inhibit the V27A M2 virus in vitro.
Article
Optics
Nathan Dostart, Hayk Gevorgyan, Deniz Onural, Milos A. Popovic
Summary: The study demonstrates a non-reciprocal element made up of a pair of microring modulators and a microring phase shifter in an active silicon photonic process, achieving an on-chip isolator. Isolation of up to 13 dB was achieved with an insertion loss of 18 dB. The design, along with increased modulation efficiency, could potentially make modulator-based isolators a standard 'black-box' component in integrated photonics CMOS foundry platform component libraries.
Article
Optics
Hayk Gevorgyan, Anatol Khilo, Mark T. Wade, Vladimir M. Stojanovi, Milos A. Popovi
Summary: This paper introduces a co-optimized monolithic electronics-photonics platform that transforms the structure of MOS field-effect transistors into highly efficient MOS capacitor ring modulators. The modulator achieves the smallest ring cavity and the largest free spectral range in the O-band, setting a record for shift efficiency. The paper demonstrates the excellent performance of the modulator under RF drive and proves its strong nonthermal tuning mechanism.
PHOTONICS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Bishnu P. Paudel, Zhi-Qiang Xu, Slobodan Jergic, Aaron J. Oakley, Nischal Sharma, Simon H. J. Brown, James C. Bouwer, Peter J. Lewis, Nicholas E. Dixon, Antoine M. van Oijen, Harshad Ghodke
Summary: Elongation by RNA polymerase can be dynamically modulated by accessory factors, and the transcription-repair coupling factor TRCF can choose to either rescue or terminate the paused/stalled RNAPs. The mechanism for TRCF's choice remains unclear. Using single-molecule assays with Escherichia coli as a model, it was found that nucleotide-bound Mfd, a bacterial TRCF, can convert the elongation complex (EC) into a catalytically poised state, allowing the EC to restart transcription. After a prolonged residence in this state, ATP hydrolysis by Mfd leads to a remodeling of the EC and loss of the RNA transcript. Biophysical studies also revealed that the motor domain of Mfd can bind and partially melt DNA with a template strand overhang.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Optics
Bohan Zhang, Mark Schiller, Kenaish Al Qubaisi, Deniz Onural, Anatol Khilo, Michael J. Naughton, Milos A. Popovic
Summary: Researcher proposed a new type of 1D polarization-insensitive grating coupler (PIGC) that is based on a zero-birefringence subwavelength corelet waveguide. The PIGC demonstrated low insertion losses and a wide polarization dependent loss bandwidth in the telecommunications O-band.
Article
Optics
Nathan Dostart, Bohan Zhang, Michael Brand, Kenaish Al Qubaisi, Deniz Onural, Daniel Feldkhun, Milos Popovi, Kelvin Wagner
Summary: Optical phased arrays (OPAs) for 2D beam-steering are limited by wavelength, which affects field of view and efficiency. We propose a Vernier transceiver scheme that uses different periodicities to eliminate ambiguity and increase efficiency. This scheme enables dynamic Vernier and ultra-fast scanning.
Article
Multidisciplinary Sciences
Brian D. Reed, Michael J. Meyer, Valentin Abramzon, Omer Ad, Pat Adcock, Faisal R. Ahmad, Gun Alppay, James A. Ball, James Beach, Dominique Belhachemi, Anthony Bellofiore, Michael Bellos, Juan Felipe Beltran, Andrew Betts, Mohammad Wadud Bhuiya, Kristin Blacklock, Robert Boer, David Boisvert, Norman D. Brault, Aaron Buxbaum, Steve Caprio, Changhoon Choi, Thomas D. Christian, Robert Clancy, Joseph Clark, Thomas Connolly, Kathren Fink Croce, Richard Cullen, Mel Davey, Jack Davidson, Mohamed M. Elshenawy, Michael Ferrigno, Daniel Frier, Saketh Gudipati, Stephanie Hamill, Zhaoyu He, Sharath Hosali, Haidong Huang, Le Huang, Ali Kabiri, Gennadiy Kriger, Brittany Lathrop, An Li, Peter Lim, Stephen Liu, Feixiang Luo, Caixia Lv, Xiaoxiao Ma, Evan McCormack, Michele Millham, Roger Nani, Manjula Pandey, John Parillo, Gayatri Patel, Douglas H. Pike, Kyle Preston, Adeline Pichard-Kostuch, Kyle Rearick, Todd Rearick, Marco Ribezzi-Crivellari, Gerard Schmid, Jonathan Schultz, Xinghua Shi, Badri Singh, Nikita Srivastava, Shannon F. Stewman, T. R. Thurston, Philip Trioli, Jennifer Tullman, Xin Wang, Yen-Chih Wang, Eric A. G. Webster, Zhizhuo Zhang, Jorge Zuniga, Smita S. Patel, Andrew D. Griffiths, Antoine M. Van Oijen, Michael McKenna, Matthew D. Dyer, Jonathan M. Rothberg
Summary: This study presents a dynamic approach for single-molecule protein sequencing, where single peptides are probed in real time using a mixture of dye-labeled amino acid recognizers and simultaneously cleaved by aminopeptidases. The peptide sequence is identified by measuring fluorescence intensity, lifetime, and binding kinetics. This method enables discrimination of single amino acid substitutions and posttranslational modifications.
Article
Optics
Kenaish Al Qubaisi, Mark Schiller, Bohan Zhang, Deniz Onural, Michael J. Naughton, Milos A. Popovic
Summary: We present the design, fabrication, and experimental characterization of photonic crystal nanobeam cavities with the smallest footprint, largest intrinsic quality factor, and smallest mode volume to date in a monolithic CMOS platform. Two types of cavities with opposite spatial mode symmetries were designed. The nanobeam cavities can be used in reflectionless topologies due to their opposite mode symmetry and evanescent coupling, making them desirable for complex photonic integrated circuits (PICs). The devices were fabricated in a 45 nm monolithic electronics-photonics CMOS platform optimized for silicon photonics (GlobalFoundries 45CLO) and demonstrated quality factors exceeding 100,000, the highest reported among fully cladded PhC nanobeam cavities in any silicon-on-insulator (SOI) platform. The ability of the cavities to confine light into small mode volumes was experimentally confirmed using near-field scanning optical microscopy (NSOM). These cavities are an important step towards realizing ultra-low energy active devices for next-generation integrated optical links beyond current microring resonator-based links and other CMOS PICs.
Article
Multidisciplinary Sciences
Yichen Zhong, Hakimeh Moghaddas Sani, Bishnu P. Paudel, Jason K. K. Low, Ana P. G. Silva, Stefan Mueller, Chandrika Deshpande, Santosh Panjikar, Xavier J. Reid, Max J. Bedward, Antoine M. van Oijen, Joel P. Mackay
Summary: CHD4 is an essential ATP-dependent translocase that alters chromatin accessibility by repositioning histone octamers. The N-terminal intrinsically disordered region (IDR) promotes remodelling integrity, while the C-terminal region harbours an auto-inhibitory region that is relieved by binding to substrate DNA.
NATURE COMMUNICATIONS
(2022)
Article
Infectious Diseases
Caitlin Keighley, Antoine M. van Oijen, Stuart J. Brentnall, Martina Sanderson-Smith, Peter Newton, Spiros Miyakis
Summary: The study found similar trends in antimicrobial resistance (AMR) among urinary Escherichia coli isolates from a private community-based laboratory and a public hospital-based laboratory in an Australian local health district. AMR rates increased over time in both settings, with consistently higher rates in the public hospital-based laboratory. Interventions targeting the community-based laboratory setting are crucial for addressing AMR in the community.
JOURNAL OF GLOBAL ANTIMICROBIAL RESISTANCE
(2022)
Article
Multidisciplinary Sciences
Nicholas R. Marzano, Bishnu P. Paudel, Antoine M. van Oijen, Heath Ecroyd
Summary: The study used total internal reflection fluorescence (TIRF) microscopy and single-molecule fluorescence resonance energy transfer (smFRET) to observe the folding process of firefly luciferase proteins mediated by the bacterial Hsp70 system. The researchers found that there are multiple cycles of chaperone binding and release to individual clients during refolding, and high rates of chaperone cycling improve refolding yield. Additionally, they discovered that DnaJ remodels misfolded proteins through a conformational selection mechanism, while DnaK resolves misfolded states through mechanical unfolding. This study elucidates important mechanistic details of chaperone-assisted folding that are inaccessible using other methods.
Proceedings Paper
Computer Science, Hardware & Architecture
D. Kramnik, I. Wang, J. M. Fargas Cabanillas, A. Ramesh, S. Buchbinder, P. Zarkos, C. Adamopoulos, P. Kumar, M. A. Popovic, V. Stojanovic
Summary: Integrated photonics offers scalability for practical photonic quantum information processing. By integrating circuits alongside photonics in a standard CMOS process, we demonstrate feedback control of four-wave mixing in a silicon microring, enabling in-situ operation in the photon-pair generation regime.
ESSCIRC 2022- IEEE 48TH EUROPEAN SOLID STATE CIRCUITS CONFERENCE (ESSCIRC)
(2022)
Proceedings Paper
Engineering, Electrical & Electronic
Kenaish Al Qubaisi, Dorde Gluhovic, Deniz Onural, Milos A. Popovic
Summary: This study proposes a scheme using microring resonators to achieve standing-wave resonator operation, eliminating reflections while maintaining a throughport response similar to a traveling-wave resonator. This could potentially enable interdigitated p-n junction microring modulators to achieve higher performance than other geometries.
2022 OPTICAL FIBER COMMUNICATIONS CONFERENCE AND EXHIBITION (OFC)
(2022)
Proceedings Paper
Engineering, Electrical & Electronic
Kenaish Al Qubaisi, Anatol Khilo, Hayk Gevorgyan, Milos A. Popovic
Summary: This article presents microring modulators in the new 45CLO photonics-optimized 45 nm electronic-photonic CMOS platform. Interdigitated disk and vertical-junction rib microring designs are demonstrated, achieving a 20 GHz bandwidth at a 25 Gbps data rate.
2021 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO)
(2021)
Proceedings Paper
Engineering, Electrical & Electronic
Josep M. Fargas Cabanillas, Manuj Kumar Singh, Bohan Zhang, Milos A. Popovi
Summary: The novel compact, ultra-broadband PSR based on photonic magic-T and RAMS demonstrates excellent performance with low polarization crosstalk and significantly reduced length compared to conventional adiabatic PSRs.
2021 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO)
(2021)
Proceedings Paper
Engineering, Electrical & Electronic
Josep M. Fargas Cabanillas, Bohan Zhang, Milos A. Popovic
Summary: The concept of rapid adiabaticity is utilized to create a mode evolution based two-spatial-mode mux-demux chain, which is four times shorter than traditional adiabatic devices, with excellent performance.
2021 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO)
(2021)