A5061588839- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Molecular Junctions and Nanostructures
- Immunotherapy and Immune Responses
- COVID-19 epidemiological studies
- Supramolecular Chemistry and Complexes
- vaccines and immunoinformatics approaches
- Nanopore and Nanochannel Transport Studies
- Force Microscopy Techniques and Applications
- Animal Virus Infections Studies
- Protein purification and stability
- Micro and Nano Robotics
- HIV Research and Treatment
- ATP Synthase and ATPases Research
- Poxvirus research and outbreaks
- stochastic dynamics and bifurcation
- Virus-based gene therapy research
- Protein Structure and Dynamics
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
- Microtubule and mitosis dynamics
- Mathematical and Theoretical Epidemiology and Ecology Models
- Advanced biosensing and bioanalysis techniques
- Evolution and Genetic Dynamics
- Machine Learning in Materials Science
York University
2021-2025
Simon Fraser University
2017-2024
University of Alberta
2023
University of Calgary
2023
Burnaby Hospital
2020
McMaster University
2017
Abstract Inspired by biology, great progress has been made in creating artificial molecular motors. However, the dream of harnessing proteins – building blocks selected nature to design autonomous motors so far remained elusive. Here we report synthesis and characterization Lawnmower, an autonomous, protein-based motor comprised a spherical hub decorated with proteases. Its “burnt-bridge” motion is directed cleavage peptide lawn, promoting towards unvisited substrate. We find that Lawnmowers...
The lipid nanoparticle (LNP)-formulated mRNA vaccines BNT162b2 and mRNA-1273 are a widely adopted multi vaccination public health strategy to manage the COVID-19 pandemic. Clinical trial data has described immunogenicity of vaccine, albeit within limited study time frame. Here, we use within-host mathematical model for LNP-formulated vaccines, informed by available clinical from 2020 September 2021, project longer term understanding immunity as function vaccine type, dosage amount, age, sex....
Our findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control and shared CD4 CD8 immunodominant epitopes seasonal coronaviruses or SARS-CoV-1, they indicate robust persistence memory at least 1 year after infection. should inform future strategies to induce vaccines against other coronaviruses.
Abstract SARS-CoV-2 lipid nanoparticle mRNA vaccines continue to be administered as the predominant prophylactic measure reduce COVID-19 disease pathogenesis. Quantifying kinetics of secondary immune response from subsequent doses beyond primary series and understanding how dose-dependent waning vary a function age, sex, various comorbidities remains an important question. We study anti-spike IgG in 152 individuals who received mRNA-based (first two doses) subset 137 then booster dose. find...
Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity these vaccines their effects on reservoirs are not available. Our study 68 PWH 23 HIV-negative participants aged 55 older post-three vaccine doses showed equally strong anti-spike IgG responses in serum saliva through week 48 from baseline, while salivary IgA low. had diminished live-virus neutralization after two doses, which 'rescued' post-booster....
The contributions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells to vaccine efficacy and durability are unclear. We investigated relationships between mRNA vaccine-induced spike-specific interferon- gamma (IFN-γ) interleukin-2 (IL-2) T-cell responses neutralizing antibody development in long-term care home staff doubly vaccinated with BNT162b2 or mRNA-1273. impacts pre-existing cross-reactive immunity on cellular humoral vaccination were additionally...
The human immune system is intrinsically variable and remarkably diverse across a population. response to antigens driven by complex interplay of time-dependent interdependencies components the system. After repeated vaccination, humoral cellular arms display highly heterogeneous dynamics, further complicating attribution phenotypic outcome specific components. We employ random forest (RF) approach classify informative differences in immunogenicity between older people living with HIV (PLWH)...
During the SARS-CoV-2 global pandemic, several vaccines, including mRNA and adenovirus vector approaches, have received emergency or full approval. However, supply chain logistics hampered vaccine delivery, which is impacting mass vaccination strategies. Recent studies identified different strategies for dose administration so that constraints issues are diminished. These include increasing time between consecutive doses in a two-dose regimen reducing dosage of second dose. We consider both...
Nature utilizes the burnt bridges ratchet (BBR) to generate active motion in a variety of biological contexts. Here, influence substrate stiffness on spherical BBR dynamics is investigated.
Despite a relatively low mutation rate, the large number of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections has allowed for substantial genetic change, leading to multitude emerging variants. Using recently determined rate (per site replication), as well within-host parameter estimates symptomatic SARS-CoV-2 infection, we apply stochastic transmission-bottleneck model describe survival probability
The burnt-bridges ratchet (BBR) mechanism is a model for biased molecular motion whereby the construct destroys track binding sites as it progresses, and therefore acts diffusing forager, seeking new substrate sites. Using Monte Carlo simulations that implement Gillespie algorithm, we investigate kinetic characteristics of simple polyvalent BBRs they move on tracks increasing width. We find width increased remain nearly ballistic considerable widths proportional to span (leg length) walker,...
Many experiments and applications require the chemical coupling of target molecules to surfaces, during which elimination nonspecific interactions presents a difficult challenge. We report on technologically accessible surface passivation conjugation method based an NHS end-labeled F127 Pluronic block copolymer (F127-NHS). To quantify between F127-NHS magnetic microspheres, we developed simple assay: microsphere adhesion by gravity, inversion, then counting, or "MAGIC" assay. improve...
The mean-squared displacement (MSD) is an averaged quantity widely used to assess anomalous diffusion. In many cases, such as molecular motors with finite processivity, the dynamics of system interest produce trajectories varying duration. Here, we explore effects processivity on different measures MSD. We do so by investigating a deceptively simple dynamical system: one-dimensional random walk (with equidistant jump lengths, symmetric move probabilities, and constant step duration)...
Abstract To design an artificial protein-based molecular motor that can autonomously step along a track is key challenge of protein and synthetic biology. We lay out roadmap for how to achieve this aim, based on modular approach combines the use natural, non-motor proteins with de novo design. define what be considered constitute successful motor, identify steps path these designs, provide vision future beyond aim.
We present here a model for multivalent diffusive transport whereby central point-like hub is coupled to multiple feet, which bind complementary sites on two-dimensional landscape. The available number of binding interactions dependent the feet (multivalency), and their allowed distance from (span). Using Monte Carlo simulations that implement Gillespie algorithm, we simulate processes 100 distinct walker designs. Informed by our simulation results derive an analytical expression diffusion...
Abstract A compartment model for an in-host liquid nanoparticle delivered mRNA vaccine is presented. Through non-dimensionalisation, five timescales are identified that dictate the lifetime of in-host: decay interferon gamma, antibody priming, autocatalytic growth, peak and decay, interleukin cessation. asymptotic analysis we able to obtain semi-analytical solutions in each time regimes which allows us predict maximal concentrations better understand parameter dependence model. We compare...
Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity these vaccines their effects on reservoirs are not available. We followed 68 PWH aged 55 older 23 age-matched HIV-negative 48 weeks from first vaccine dose, after total three doses. All antiretroviral therapy (cART) had different immune status, including responders (IR), non-responders (INR), low-level viremia (LLV). measured neutralizing Ab responses to...
Abstract Cellular-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 SARS-CoV-2-infected survivors over a one year post symptom onset (PSO) interval by ex vivo cytokine ELISpot assay. All subjects demonstrated SARS-CoV-2-specific IFN-γ, IL-2, and Granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced CD4+ cells, targeted all structural proteins...
Abstract SARS-CoV-2 lipid nanoparticle mRNA therapeutics continue to be administered as the predominant therapeutic intervention reduce COVID-19 disease pathogenesis. Quantifying kinetics of secondary immune response from subsequent doses beyond primary series, and understanding how dose-dependent waning vary a function age, sex, various comorbidities, remains an important question. We study anti-spike IgG in 152 individuals who received mRNA-based series subset 137 then booster dose. find...