Sara Capponi

• Dr.
• Researcher at IBM

The vast and complex materials design space demands innovative strategies to integrate multidisciplinary scientific knowledge and optimize materials discovery. While large language models (LLMs) have demonstrated promising reasoning and automation capabilities across various domains, their application in materials science remains limited due to a l...

Repurposing an organelle for specialized metabolism provides an avenue for fermentable, unicellular organisms such as Saccharomyces cerevisiae to mimic compartmentalization of metabolic pathways within different plant tissues. Peroxisomes are attractive organelles for repurposing as they are not required for yeast viability when grown on glucose an...

The fruit fly, Drosophila melanogaster, is an experimentally tractable model system that has recently emerged as a powerful “new approach methodology” (NAM) for chemical safety testing. As oogenesis is well conserved at the molecular and cellular level, measurements of Drosophila fecundity can be useful for identifying chemicals that affect reprodu...

A partnership between four universities, an industrial research lab, and a public science museum, created as a National Science Foundation Science and Technology Center, offers diverse collaboration and learning opportunities in cellular engineering. Each institution plays a vital role: universities advance science education, industry develops and...

Measurements of Drosophila fecundity are used in a wide variety of studies, such as investigations of stem cell biology, nutrition, behavior, and toxicology. In addition, because fecundity assays are performed on live flies, they are suitable for longitudinal studies such as investigations of aging or prolonged chemical exposure. However, standard...

A central role of viral capsids is to protect the viral genome from the harsh extracellular environment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. In this study, we genetically perturb this equ...

The relationship between the genotype, the set of instructions encoded into a genome, and the phenotype, the macroscopic realization of those instructions, has not been fully explored. This is mostly due to the general absence of tools capable of uncovering this relationship. In this work, we develop an unsupervised learning framework relating chan...

Biophysics is an interdisciplinary pursuit requiring researchers with knowledge and skills in several areas. Optical instruments and computers are fundamental tools in biophysics research to collect and analyze data. We developed a 1-semester Optical Engineering Laboratory course to teach image processing, optical engineering, and research skills t...

In recent years, there has been tremendous progress in the development of quantum computing hardware, algorithms and services leading to the expectation that in the near future quantum computers will be capable of performing simulations for natural science applications, operations research, and machine learning at scales mostly inaccessible to clas...

Cell therapies are powerful technologies in which human cells are reprogrammed for therapeutic applications such as killing cancer cells or replacing defective cells. The technologies underlying cell therapies are increasing in effectiveness and complexity, making rational engineering of cell therapies more difficult. Creating the next generation o...

Chimeric antigen receptor (CAR) costimulatory domains derived from native immune receptors steer the phenotypic output of therapeutic T cells. We constructed a library of CARs containing ~2,300 synthetic costimulatory domains, built from combinations of 13 signaling motifs. These CARs promoted diverse cell fates, which were sensitive to motif combi...

A central role of viral capsids is to protect the viral genome from the harsh extracellular environ-ment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell en-try. In this study, we genetically perturbed this...

A central role of viral capsids is to protect the viral genome from the harsh extracellular environment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. In this study, we genetically perturbed this e...

Epitopes are short amino acid sequences that define the antigen signature to which an antibody or T cell receptor binds. In light of the current pandemic, epitope analysis and prediction are paramount to improving serological testing and developing vaccines. In this paper, known epitope sequences from SARS-CoV, SARS-CoV-2, and other Coronaviridae w...

The relationship between the genotype, the genetic instructions encoded into a genome, and phenotype, the macroscopic realization of such instructions, remains mostly uncharted. In addition, tools able to uncover the connection between the phenotype with a specific set of responsible genes are still under definition. In this work, we focus on yeast...

Epitopes are short amino acid sequences that define the antigen signature to which an antibody binds. In light of the current pandemic, epitope analysis and prediction is paramount to improving serological testing and developing vaccines. In this paper, we leverage known epitope sequences from SARS-CoV, SARS-CoV-2 and other Coronaviridae and use th...

The YidC family of proteins are membrane insertases that catalyze the translocation of the periplasmic domain of membrane proteins via a hydrophilic groove located within the inner leaflet of the membrane. All homologs have a strictly conserved, positively charged residue in the center of this groove. In B. subtilis, the positively charged residue...

Chimeric antigen receptor (CAR) costimulatory domains steer the phenotypic output of therapeutic T cells. In most cases these domains are derived from native immune receptors, composed of signaling motif combinations selected by evolution. To explore if non-natural combinations of signaling motifs could drive novel cell fates of interest, we constr...

The COVID-19 pandemic still affects us all. But how much can we rely on social distancing and face masks to protect ourselves?

RNA viruses generate defective viral genomes (DVG) that can interfere with replication of the parental wild-type virus. To examine their therapeutic potential, we created a DVG by deleting the capsid-coding region of poliovirus. Strikingly, intraperitoneal or intranasal administration of this genome, which we termed eTIP1, elicits an antiviral resp...

We present a novel technique to predict binding affinity trends between two molecules from atomistic molecular dynamics simulations. The technique uses a neural network algorithm applied to a series of images encoding the distance between two molecules in time. We demonstrate that our algorithm is capable of separating with high accuracy non-hydrop...

COVID-19’s high virus transmission rates have caused a pandemic that is exacerbated by the high rates of asymptomatic and presymptomatic infections. These factors suggest that face masks and social distance could be paramount in containing the pandemic. We examined the efficacy of each measure and the combination of both measures using an agent-bas...

Despite extended experimental and computational studies, the mechanism regulating membrane protein folding and stability in cell membranes is not fully understood. In this review, I will provide a personal and partial account of the scientific efforts undertaken by Dr. Stephen White to shed light on this topic. After briefly describing the role of...

We present a novel technique to predict binding affinity trends between two molecules from atomistic molecular dynamics simulations. The technique uses a neural network algorithm applied to a series of images encoding the distance between two molecules in time. We demonstrate that our algorithm is capable of separating with high accuracy mutations...

K 2P potassium channels regulate cellular excitability using their selectivity filter (C-type) gate. C-type gating mechanisms, best characterized in homotetrameric potassium channels, remain controversial and are attributed to selectivity filter pinching, dilation, or subtle structural changes. The extent to which such mechanisms control C-type gat...

The COVID-19 global crisis is facilitated by high virus transmission rates and high percentages of asymptomatic and presymptomatic infected individuals. Containing the pandemic hinged on combinations of social distancing and face mask use. Here we examine the efficacy of these measures, using an agent-based modeling approach that evaluates face mas...

Enterovirus (EV)-D68 has been associated with epidemics in the United Sates in 2014, 2016 and 2018. This study aims to identify potential viral virulence determinants. We found that neonatal type I interferon receptor knockout mice are susceptible to EV-D68 infection via intraperitoneal inoculation and were able to recapitulate the paralysis proces...

Molecular dynamics simulations of poly(vinyl methyl ether) in aqueous solution with weight concentration cw = 30% were performed in a wide temperature range by simulated cooling between 400 and 175 K. A shift of glass transition temperature due to plasticization effect is observed with the decrease of simulated TgMD by 25 K as compared to pure PVME...

K2P channels regulate nervous, cardiovascular, and immune system functions1,2 through the action of their selectivity filter (C type) gate3-6. Although structural studies show K2P conformations that impact activity7-13, no selectivity filter conformational changes have been observed. Here, combining K2P2.1 (TREK 1) X ray crystallography in differen...

Our senses of touch and hearing are dependent on the conversion of external mechanical forces into electrical impulses by the opening of mechanosensitive channels in sensory cells. This remarkable feat involves the conversion of a macroscopic mechanical displacement into a subnanoscopic conformational change within the ion channel. The mechanosensi...

In this simulation study, we investigate the influence of biomolecular confinement on dynamical processes in water. We compare water confined in a membrane protein nanopore at room temperature to pure liquid water at low temperatures with respect to structural relaxations, intermolecular vibrations, and the propagation of collective modes. We obser...

The YidC/Oxa1/Alb3 family of membrane proteins function to insert proteins into membranes in bacteria, mitochondria, and chloroplasts. Recent X-ray structures of YidC from Bacillus halodurans and Escherichia coli revealed a hydrophilic groove that is accessible from the lipid bilayer and the cytoplasm. Here, we explore the water accessibility withi...

Organized as bilayers, phospholipids are the fundamental building blocks of cellular membranes and determine many of their biological functions. Interactions between the two leaflets of the bilayer (interleaflet coupling) have been implicated in the passage of information through membranes. However, physically, the meaning of interleaflet coupling...

Clusters of charged groups on the surface of proton-transfer proteins may participate in proton transfers. PsbO, an extrinsic subunit of photosystem II, is a carboxylate-rich protein part of an extensive hydrogen-bond network leading to the catalytic site. This raises the important question as to whether specific clusters of carboxylate groups on t...

Significance α-Helical membrane proteins are assembled cotranslationally into cell membranes with the aid of the heterotrimeric membrane-embedded translocon complex. The structures of several translocons reveal that the interior has an hourglass shape filled with water. Because nascent peptide chains emerging from the ribosome are thought to pass t...

SecY constitutes the core of the highly conserved SecYEG translocon complex that governs the translocation or integration of proteins across or into cytoplasmic membranes. Besides its role of guiding nascent membrane protein chains into the lipid bilayer, it also plays an important role in determining transmembrane topology via the so-called positi...

In bacteria and archea, the insertion of membrane proteins into the plasma membrane is governed by the SecY translocon complex. Understanding how the SecY translocon distinguishes a transmembrane (TM) segment from a secretory one is therefore of the utmost importance. The process of insertion of a TM segment into the membrane resembles a thermodyna...

(2)H-nuclear magnetic resonance (NMR) and neutron scattering (NS) on isotopically labelled samples have been combined to investigate the structure and dynamics of polyvinylpyrrolidone (PVP) aqueous solutions (4 water molecules/monomeric unit). Neutron diffraction evidences the nanosegregation of polymer main-chains and water molecules leading to th...

We present a quasielastic neutron scattering (QENS) investigation of the component dynamics in an aqueous Poly(vinyl methyl ether) (PVME) solution (30% water content in weight). In the glassy state, an important shift in the Boson peak of PVME is found upon hydration. At higher temperatures, the diffusive-like motions of the components take place w...

In the present work, we focus on the free volume evaluations from different points of view, including the aspect of probe sizes, temperature, and cavity threshold. The free volume structure is analyzed on structures of poly(vinyl methylether) prepared by fully atomistic molecular dynamics. At first, the temperature behavior of an overall free volum...

Quasielastic neutron scattering experiments (time-of-flight, neutron spin echo, and backscattering) on protonated poly(vinyl methyl ether) (PVME) have revealed the hydrogen dynamics above the glass-transition temperature. Fully atomistic molecular dynamics simulations properly validated with the neutron scattering results have allowed further chara...

In this work we analyze and compare the free volume of a polymer system poly(vinyl methylether) (PVME) at 300 K obtained by the two direct but different approaches: Positron annihilation lifetime spectroscopy (PALS) and computer simulations. The free volume is calculated from the simulated cells of PVME by means of numerical methods based on grid s...

In this contribution we present a developed method for determination of the shape specificity of the free volume cavities, along with free volume characteristics, computed on the microstructure of poly-vinyl-methyl-ether at 300 K prepared by molecular dynamics simulations. The free volume microstructure was found to be percolated for small probes a...

Through elastic neutron scattering measurements, we investigated the thermal fluctuations of DNA enclosed by glycerol-water glassy matrices, at different levels of hydration, over the wide temperature range from 20 to 300 K. For all the samples, the extracted hydrogen mean square displacements (MSD) show a purely vibrational harmonic trend at very...

Using elastic neutron scattering measurements we have investigated the picosecond dynamics of dry and hydrated powders of DNA in the double-stranded (dsDNA) and single-stranded (ssDNA) state in the temperature range from 20 to 300 K. The extracted mean square displacements of DNA hydrogen atoms exhibit an onset of anharmonicity at around 100 K. The...