Article
Multidisciplinary Sciences
Ilya A. Vakser, Sergei Grudinin, Nathan W. Jenkins, Petras J. Kundrotas, Eric J. Deeds
Summary: Computational methodologies are being used to model the entire cell at the molecular level. This study combines protein docking and molecular simulations to develop an approach that can simulate cellular processes at unprecedented timescales and all-atom resolution. The approach successfully captures the dynamics of protein interactions and has been validated across various protein systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Editorial Material
Genetics & Heredity
Marja C. P. Timmermans
Summary: Marja Timmermans recalls a series of papers published in consecutive order in the journal Science in 2018, which reported the utilization of single-cell RNA sequencing to obtain a more comprehensive understanding of the expression landscapes during early vertebrate development.
NATURE REVIEWS GENETICS
(2023)
Article
Mathematics, Applied
Andrew Cleary, Jacob Page
Summary: This paper presents a new method for systematically exploring the free-energy landscape in the study of superfluids. It discovers new equilibrium states and evaluates the likelihood of observing certain states in experiments. Additionally, it investigates the dynamics near the minimizing state.
Article
Chemistry, Multidisciplinary
Rashik Ahmed, Jinfeng Huang, Madoka Akimoto, Tongyu Shi, Giuseppe Melacini
Summary: The study demonstrates that temperature has a significant impact on N-15 - R-2, effectively identifying self-association sites. Through agglomerative clustering, the experiment systematically examines the network of residues involved in self-association and extracts the hierarchy of alpha S self-association sites.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Samuel Nayler, Devika Agarwal, Fabiola Curion, Rory Bowden, Esther B. E. Becker
Summary: By utilizing a robust method without the need for mouse co-culture, three-dimensional cerebellar organoids were successfully generated from human pluripotent stem cells (hPSCs), displaying hallmarks of in vivo cerebellar development. Single-cell profiling revealed the presence and maturity of transcriptionally distinct populations encompassing major cerebellar cell types. This xeno-free human cerebellar organoid model provides valuable insight into cerebellar development and associated disorders through enrichment of cerebellar disease genes in distinct cell populations.
SCIENTIFIC REPORTS
(2021)
Article
Biotechnology & Applied Microbiology
Douyue Li, Saichao Pan, Hongxi Zhang, Yongzhuo Fu, Zhuli Peng, Liang Zhang, Shan Peng, Fei Xu, Hanrou Huang, Ruixue Shi, Heping Zheng, Yousong Peng, Zhongyang Tan
Summary: The study established 540 maps displaying the distributional features of SSRs in human Y-DNA at chromosomal level. The maps revealed significant SSR accumulation in certain bins, as well as sparse distributions in others, challenging the widely accepted view of SSR-rich regions in noncoding and intergenic regions of the Y-DNA. Furthermore, the study suggests biological significance and calls for further analysis of the huge number of SSRs in human Y-DNA.
Review
Cell Biology
Robert G. Kelly
Summary: Organogenesis requires the coordinated development of multiple cell lineages that converge, interact, and specialize to form functional structures, such as the heart. Recent single-cell transcriptomic analyses and genetic tracing experiments have provided insights into the origin and developmental trajectories of cardiac progenitor cells. This knowledge is essential for addressing challenges in cardiac biology and disease.
DEVELOPMENTAL CELL
(2023)
Article
Hematology
Raymond T. Doty, Christopher G. Lausted, Adam D. Munday, Zhantao Yang, Xiaowei Yan, Changting Meng, Qiang Tian, Janis L. Abkowitz
Summary: The anemias of myelodysplastic syndrome (MDS) and Diamond Blackfan anemia (DBA) are macrocytic and result from diverse genetic mutations. The fate of single erythroid marrow cells from individuals with DBA or MDS-5q was studied to understand shared mechanisms that lead to cell death. It was found that cell death occurs much later after cells upregulate transferrin receptor and initiate heme synthesis. Cells destined to die express high levels of heme-responsive genes, while surviving cells downregulate heme synthesis and upregulate DNA damage response, hypoxia, and HIF1 pathways.
Article
Multidisciplinary Sciences
Feng Zhi, Bowen Li, Chuanxia Zhang, Fan Xia, Rong Wang, Weihong Xie, Sihui Cai, Dawei Zhang, Ren Kong, Yiqiao Hu, Yilin Yang, Ya Peng, Jun Cui
Summary: NLRP6 enhances the PI3K/AKT pathway by binding and degrading p85 alpha, promoting tumorigenesis. The interaction between NLRP6 and p85 alpha offers a potential therapeutic target for tumor treatment.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Qing Liu, Zhe Liang, Dan Feng, Sanjie Jiang, Yifan Wang, Zhuoying Du, Ruoxi Li, Guihua Hu, Pingxian Zhang, Yanfei Ma, Jan U. Lohmann, Xiaofeng Gu
Summary: This study analyzed the transcriptomes of rice root tip cells, identifying major cell types and defining novel cell-type-specific marker genes for two cultivars. The research found divergent cell types associated with phytohormone biosynthesis, signaling, and response in rice. Significant differences in cell-type transcript profiles between Arabidopsis and rice were also detected, emphasizing the importance of analyzing tissues across diverse model species.
Article
Cell Biology
Mengmeng Jiang, Yanyu Xiao, E. Weigao, Lifeng Ma, Jingjing Wang, Haide Chen, Ce Gao, Yuan Liao, Qile Guo, Jinrong Peng, Xiaoping Han, Guoji Guo
Summary: Utilizing Microwell-seq technology, researchers analyzed over 250,000 single cells of zebrafish, revealing the single-cell compositions of 18 tissue types, including both embryo and adult stages. Through studying caudal fin regeneration, unique characteristics of blastema population and key genetic regulations in zebrafish tissue repair were identified. This single-cell dataset demonstrates the utility of zebrafish cell landscape resources in various fields of biological research.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Michael W. Dorrity, Cristina M. Alexandre, Morgan O. Hamm, Anna-Lena Vigil, Stanley Fields, Christine Queitsch, Josh T. Cuperus
Summary: The study reports the regulatory landscape of Arabidopsis thaliana roots at single-cell resolution and identifies thousands of differentially accessible sites. It finds that a cell's regulatory landscape and transcriptome independently capture cell type identity, and leveraging this information to integrate data helps characterize developmental progression and cell division. The approach provides an analytical framework to infer the gene regulatory networks that execute plant development.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Yang Chen, Shaofei Tong, Yuanzhong Jiang, Fandi Ai, Yanlin Feng, Junlin Zhang, Jue Gong, Jiajia Qin, Yuanyuan Zhang, Yingying Zhu, Jianquan Liu, Tao Ma
Summary: This study utilized optimized single-cell RNA sequencing technology to reveal the transcriptional landscape of cell types in highly lignified poplar stems. Different cell clusters with distinct phytohormone response patterns were identified, allowing reconstruction of cell differentiation trajectories involved in phloem and xylem development.
Article
Biochemistry & Molecular Biology
Jose A. Villegas, Tasneem M. Vaid, Michael E. Johnson, Terry W. Moore
Summary: A major challenge in computational modeling of macromolecules is the vast conformational space due to atomic degrees of freedom. Recent interest in predictive models of complexes mediated by PROTACs led to the application of advanced computational techniques. However, repurposing existing tools for protein-protein docking and linker conformer generation results in incompatible structures. In this study, a cyclic coordinate descent algorithm was used to position PROTACs into complex-bound configurations, allowing for a restricted search in protein-protein conformations that can be bridged by a PROTAC molecule with a given linker composition.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Optics
Romanus Hutchins, Giulia Zanini, Giuliano Scarcelli
Summary: Spectral imaging techniques utilize dispersive elements and optical microscopes to extract spectral information. High-speed acquisition of spectral information has been achieved through multiplexing in hyperspectral imaging, Raman imaging, and Brillouin imaging. This paper extends 2D multiplexing to high spectral resolutions of approximately 80 MHz (approximately 0.0001 nm) using high-throughput spectral discrimination based on atomic transitions.
Article
Physics, Condensed Matter
Thomas E. Videbaek, Huang Fang, Daichi Hayakawa, Botond Tyukodi, Michael F. Hagan, W. Benjamin Rogers
Summary: The ability to design and synthesize complicated colloidal particles allows for the self-assembly of complex structures, but thermal fluctuations can lead to off-target assembly. This study investigates strategies to limit off-target assembly by using multiple types of subunits, and shows how the assembly specificity can be improved by introducing tiling rules for assembling tubules from multiple species of triangles.
JOURNAL OF PHYSICS-CONDENSED MATTER
(2022)
Article
Mechanics
Caleb G. Wagner, Michael F. Hagan, Aparna Baskaran
Summary: Active Brownian particles are minimal models for self-propelled colloids in dissipative environments. In the presence of boundaries and obstacles, these systems approach nontrivial nonequilibrium steady states with interesting phenomena such as accumulation at boundaries, ratchet effects, and long-range depletion interactions. However, theoretical analysis of these phenomena has been challenging. This study addresses this challenge by proposing an approximation strategy that connects asymptotic solutions of the Smoluchowski equation to boundary conditions.
JOURNAL OF STATISTICAL MECHANICS-THEORY AND EXPERIMENT
(2022)
Article
Physics, Multidisciplinary
Linnea M. Lemma, Michael M. Norton, Alexandra M. Tayar, Stephen J. DeCamp, S. Ali Aghvami, Seth Fraden, Michael F. Hagan, Zvonimir Dogic
Summary: The study quantified the motion of microtubule bundles, revealing that the extension speed of isolated bundles is faster than that in dense active nematics. In the dense active nematic, the sliding speeds of filaments are widely distributed, showing both contractile and extensile relative motion.
PHYSICAL REVIEW LETTERS
(2021)
Article
Multidisciplinary Sciences
Matthew S. E. Peterson, Aparna Baskaran, Michael F. Hagan
Summary: The researchers propose a framework to control shape transformations and filament organization in deformable vesicles, using simulations to reveal various filament spatiotemporal organizations arising from the interplay between active stress and deformability of the confinement. These emerging behaviors have not been observed in traditional systems, providing insights for designing active materials with targeted shape dynamics.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Botond Tyukodi, Farzaneh Mohajerani, Douglas M. Hall, Gregory M. Grason, Michael F. Hagan
Summary: This study investigates the assembly thermodynamics of a particle-based model for geometrically frustrated assembly using computational modeling. The results show the occurrence of finite-temperature self-limiting assembly within a certain range of parameters and identify mechanisms that promote unbounded growth.
Article
Chemistry, Physical
Lev Tsidilkovski, Farzaneh Mohajerani, Michael F. Hagan
Summary: This article presents a dynamical simulation of the assembly process of an icosahedral protein shell around a bicomponent fluid cargo. The study demonstrates that the relative interaction strengths among different cargo species are crucial in determining the encapsulation, spatial organization, and assembly pathways of the shell. The findings have implications for understanding natural microcompartments and accelerating specific reactions in synthetic biology.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Farzaneh Mohajerani, Botond Tyukodi, Christopher J. Schlicksup, Jodi A. Hadden-Perilla, Adam Zlotnick, Michael F. Hagan
Summary: In this study, computer simulations and analysis were used to reveal the assembly process of hepatitis B virus (HBV) and the mechanism of capsid polymorphism. The findings are important for understanding the HBV lifecycle and developing new antiviral drugs.
Article
Multidisciplinary Sciences
Daichi Hayakawa, Thomas E. Videbaek, Douglas M. Hall, Huang Fang, Christian Sigl, Elija Feigl, Hendrik Dietz, Seth Fraden, Michael F. Hagan, Gregory M. Grason, W. Benjamin Rogers
Summary: This article explores new design principles for making self-limiting architectures using self-assembly. The authors use DNA origami to create triangular subunits with specific interactions and binding angles, and study their assembly into tubules with a self-limited width. They demonstrate that the tubules can reach significant lengths and that their width can be controlled through geometric programming. They also find that the width and chirality of the tubules can be manipulated by increasing the number of subunit species. These findings provide insights into the role of assembly complexity and geometry in self-limiting assembly and have potential applications in other self-limiting architectures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Physical
Anthony Trubiano, Michael F. Hagan
Summary: The promise of self-assembly to enable the formation of materials with desired structures has driven efforts to uncover rational design principles. However, ensuring the accessibility of the target structure remains a challenge. In this study, the authors develop a framework combining Markov state model analysis with optimal control theory to optimize self-assembly protocols and maximize the yield of the target structure.
JOURNAL OF CHEMICAL PHYSICS
(2022)
Article
Chemistry, Multidisciplinary
Caleb A. Starr, Smita Nair, Sheng-Yuan Huang, Michael F. Hagan, Stephen C. Jacobson, Adam Zlotnick
Summary: A viral-like particles (VLPs) that can release its cargo in response to a trigger was designed by chemically redesigning the dimeric hepatitis B virus (HBV) capsid protein. The VLPs could gradually dissociate and release its contents when exposed to a reducing agent, indicating a responsive behavior to external stimuli.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Physics, Multidisciplinary
Chaitanya Joshi, Sattvic Ray, Linnea M. Lemma, Minu Varghese, Graham Sharp, Zvonimir Dogic, Aparna Baskaran, Michael F. Hagan
Summary: This study identifies optimal continuum models for active nematics directly from experimental data using sparse regression method, and achieves important findings in microtubule-based active nematics experiments.
PHYSICAL REVIEW LETTERS
(2022)
Article
Biochemical Research Methods
Michael F. Hagan, Farzaneh Mohajerani
Summary: Liquid-liquid phase separation promotes self-assembly and the formation of complex structures like virus particles. Theoretical models show that this process can accelerate assembly and prevent subunits from running out, leading to properly assembled particles. These findings have implications in the prevention and treatment of viral infections and provide insights into other self-assembly reactions in biological cells.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Caleb A. Starr, Smita Nair, Sheng-Yuan Huang, Michael F. Hagan, Stephen C. Jacobson, Adam Zlotnick
Summary: To create a virus-like particle (VLP) that can release its cargo upon triggering, a chemical biology approach is employed to destabilize a self-assembling capsid. By redesigning the dimeric hepatitis B virus (HBV) capsid protein (Cp) with differentially addressable cysteines, the resulting construct forms VLPs that can undergo triggered dissociation. The VLPs are stable until exposed to reducing agent, causing slow dissociation and release of cargo.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Physical
Huang Fang, Botond Tyukodi, W. Benjamin Rogers, Michael F. Hagan
Summary: In contrast to most self-assembling synthetic materials, biological self-assembly processes are self-limited. This article studies a class of self-closing assemblies: cylindrical tubules assembled from triangular monomers. By controlling the preferred curvature of the monomers and their interaction strengths, different size scales can be targeted in the assembly process.
Meeting Abstract
Biophysics
Farzaneh Mohajerani, Michael F. Hagan
BIOPHYSICAL JOURNAL
(2022)