scholarly journals Designed proteins assemble antibodies into modular nanocages

2020 ◽  
Author(s):  
Robby Divine ◽  
Ha V. Dang ◽  
George Ueda ◽  
Jorge A. Fallas ◽  
Ivan Vulovic ◽  
...  
Keyword(s):  
Computational Models ◽  
Computational Design ◽  
Covalent Modification ◽  
T Cell Proliferation ◽  
Surface Receptors ◽  
Form And Function ◽  
Designed Proteins ◽  
Cd40 Activation ◽  
And Function ◽  
Binding Avidity

AbstractAntibodies are widely used in biology and medicine, and there has been considerable interest in multivalent antibody formats to increase binding avidity and enhance signaling pathway agonism. However, there are currently no general approaches for forming precisely oriented antibody assemblies with controlled valency. We describe the computational design of two-component nanocages that overcome this limitation by uniting form and function. One structural component is any antibody or Fc fusion and the second is a designed Fc-binding homo-oligomer that drives nanocage assembly. Structures of 8 antibody nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage match the corresponding computational models. Antibody nanocages targeting cell-surface receptors enhance signaling compared to free antibodies or Fc-fusions in DR5-mediated apoptosis, Tie2-mediated angiogenesis, CD40 activation, and T cell proliferation; nanocage assembly also increases SARS-CoV-2 pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc-ACE2 fusion proteins. We anticipate that the ability to assemble arbitrary antibodies without need for covalent modification into highly ordered assemblies with different geometries and valencies will have broad impact in biology and medicine.

scholarly journals Designed proteins assemble antibodies into modular nanocages

Science ◽  
2021 ◽  
Vol 372 (6537) ◽  
pp. eabd9994
Author(s):  
Robby Divine ◽  
Ha V. Dang ◽  
George Ueda ◽  
Jorge A. Fallas ◽  
Ivan Vulovic ◽  
...  
Keyword(s):  
Computational Models ◽  
Death Receptor ◽  
Computational Design ◽  
Death Receptor 5 ◽  
Angiotensin Converting Enzyme 2 ◽  
Surface Receptors ◽  
Form And Function ◽  
Cd40 Activation ◽  
Multivalent Display ◽  
And Function

Multivalent display of receptor-engaging antibodies or ligands can enhance their activity. Instead of achieving multivalency by attachment to preexisting scaffolds, here we unite form and function by the computational design of nanocages in which one structural component is an antibody or Fc-ligand fusion and the second is a designed antibody-binding homo-oligomer that drives nanocage assembly. Structures of eight nanocages determined by electron microscopy spanning dihedral, tetrahedral, octahedral, and icosahedral architectures with 2, 6, 12, and 30 antibodies per nanocage, respectively, closely match the corresponding computational models. Antibody nanocages targeting cell surface receptors enhance signaling compared with free antibodies or Fc-fusions in death receptor 5 (DR5)–mediated apoptosis, angiopoietin-1 receptor (Tie2)–mediated angiogenesis, CD40 activation, and T cell proliferation. Nanocage assembly also increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus neutralization by α-SARS-CoV-2 monoclonal antibodies and Fc–angiotensin-converting enzyme 2 (ACE2) fusion proteins.

scholarly journals Generating Realistic Morphologies of Neurons in Rodent Hippocampus with DCGAN

2018 ◽  
Author(s):  
Darian H. Hadjiabadi
Keyword(s):  
Computational Models ◽  
False Positive Rate ◽  
A Priori ◽  
Image Features ◽  
Generative Adversarial Network ◽  
Dendritic Trees ◽  
Form And Function ◽  
Adversarial Network ◽  
Positive Rate ◽  
And Function

AbstractDendritic size and branching patterns are important features of neural form and function. However, current computational models of neuronal networks use simplistic cylindrical geometries to mimic dendritic arborizations. One reason for this is that current methods to generate dendritic trees have rigid a priori constraints. To address this, a deep convolutional generative adversarial network (DCGAN) trained on images of rodent hippocampal granule and pyramidal dendritic trees. Image features learned by the network were used to generate realistic dendritic morphologies. Results show that DCGANs achieved greater stability∗ and high generalization, as quantified by kernel maximum mean discrepancy, when exposed to instance noise and/or label smoothing during training. Trained models successfully generated realistic morphologies for both neuron types, with high false positive rate reported by expert reviewers. Collectively, DCGANs offer a unique opportunity to advance the geometry of neural modeling, and, therefore, to propel our understanding of neuronal function.∗ A “stable/stabilized DCGAN”, as mentioned throughout this work, is a DCGAN which was stable throughout training.

Scanning tunneling microscopy (STM) of DNA and RNA

1989 ◽  
Vol 47 ◽  
pp. 34-35
Author(s):  
Patricia G. Arscott ◽  
Gil Lee ◽  
Victor A. Bloomfield ◽  
D. Fennell Evans
Keyword(s):  
Molecular Structures ◽  
Inorganic Materials ◽  
Resolving Power ◽  
Scanning Tunneling ◽  
Tunneling Microscopy ◽  
Form And Function ◽  
Dna And Rna ◽  
Calf Thymus ◽  
And Function ◽  
The Relationship

STM is one of the most promising techniques available for visualizing the fine details of biomolecular structure. It has been used to map the surface topography of inorganic materials in atomic dimensions, and thus has the resolving power not only to determine the conformation of small molecules but to distinguish site-specific features within a molecule. That level of detail is of critical importance in understanding the relationship between form and function in biological systems. The size, shape, and accessibility of molecular structures can be determined much more accurately by STM than by electron microscopy since no staining, shadowing or labeling with heavy metals is required, and there is no exposure to damaging radiation by electrons. Crystallography and most other physical techniques do not give information about individual molecules.We have obtained striking images of DNA and RNA, using calf thymus DNA and two synthetic polynucleotides, poly(dG-me5dC)·poly(dG-me5dC) and poly(rA)·poly(rU).

Re-examining the form and function of superstition

2011 ◽  
Author(s):  
Scott Fluke ◽  
Russell J. Webster ◽  
Donald A. Saucier
Keyword(s):  
Form And Function ◽  
And Function

A New Form and Function for Personality

2013 ◽  
Author(s):  
Joshua Wilt ◽  
William Revelle
Keyword(s):  
Form And Function ◽  
New Form ◽  
And Function

Ausnahmesegment

2018 ◽  
Vol 48 (191) ◽  
Author(s):  
Barbara Schönig
Keyword(s):  
Welfare State ◽  
Social Housing ◽  
Integrated Approach ◽  
New Paradigm ◽  
Development Models ◽  
Form And Function ◽  
Institutional Organization ◽  
National Welfare ◽  
And Function ◽  
The Welfare State

Going along with the end of the “golden age” of the welfare state, the fordist paradigm of social housing has been considerably transformed. From the 1980s onwards, a new paradigm of social housing has been shaped in Germany in terms of provision, institutional organization and design. This transformation can be interpreted as a result of the interplay between the transformation of national welfare state and housing policies, the implementation of entrepreneurial urban policies and a shift in architectural and urban development models. Using an integrated approach to understand form and function of social housing, the paper characterizes the new paradigm established and nevertheless interprets it within the continuity of the specific German welfare resp. housing regime, the “German social housing market economy”.

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