Biology subjects

Ilya Nemenman

Publications and source records attributed to Ilya Nemenman.

3 recordsLinked to original sources

bioRxiv2016

Single variant bottleneck in the early dynamics of H. influenzae bacteremia in neonatal rats questions the theory of independent action

There is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (SmS and SmR) and otherwise isogenic stains of Haemophilus influenzae type b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, SmS or SmR. After rulling out other possibilities through years of related experiments, the field seems to have settled on a plausible explanation for this phenomenon: the first bacterium to invade the host activates the host immune response that shuts the door on the second invading strain. To explore this hypothesis in a necessarily quantitative way, we modeled this process with a set of mixed stochastic and deterministic differential equations. Our analysis of the properties of this model with realistic parameters suggests that this hypothesis cannot explain the experimental results of Moxon and Murphy, and in particular the observed relationship between the frequency of different types of blood infections (bacteremias) and the inoculum size. We propose modifications to the model that come closer to explaining these data. However, the modified and better fitting model contradicts the common theory of independent action of individual bacteria in establishing infections. We discuss the implications of these results.

Biophysics↗

bioRxiv2016

Motor control by precisely timed spike patterns

A fundamental problem in neuroscience is to understand how sequences of action potentials (\"spikes\") encode information about sensory signals and motor outputs. Although traditional theories of neural coding assume that information is conveyed by the total number of spikes fired (spike rate), recent studies of sensory [1-5] and motor [6] activity have shown that far more information is carried by the millisecond-scale timing patterns of action potentials (spike timing). However, it is unknown whether or how subtle differences in spike timing drive differences in perception or behavior, leaving it unclear whether the information carried by spike timing actually plays a causal role in brain function [1]. Here we demonstrate how a precise spike timing code is read out downstream by the muscles to control behavior. We provide both correlative and causal evidence to show that the nervous system uses millisecond-scale variations in the timing of spikes within multi-spike patterns to regulate a relatively simple behavior - respiration in the Bengalese finch, a songbird. These findings suggest that a fundamental assumption of current theories of motor coding requires revision, and that significant improvements in applications, such as neural prosthetic devices, can be achieved by using precise spike timing information.

Neuroscience↗

bioRxiv2015

Cell-cell communication enhances the capacity of cell ensembles to sense shallow gradients during morphogenesis

AbstractCollective cell responses to exogenous cues depend on cell-cell interactions. In principle, these can result in enhanced sensitivity to weak and noisy stimuli. However, this has not yet been shown experimentally, and, little is known about how multicellular signal processing modulates single cell sensitivity to extracellular signaling inputs, including those guiding complex changes in the tissue form and function. Here we explored if cell-cell communication can enhance the ability of cell ensembles to sense and respond to weak gradients of chemotactic cues. Using a combination of experiments with mammary epithelial cells and mathematical modeling, we find that multicellular sensing enables detection of and response to shallow Epidermal Growth Factor (EGF) gradients that are undetectable by single cells. However, the advantage of this type of gradient sensing is limited by the noisiness of the signaling relay, necessary to integrate spatially distributed ligand concentration information. We calculate the fundamental sensory limits imposed by this communication noise and combine them with the experimental data to estimate the effective size of multicellular sensory groups involved in gradient sensing. Functional experiments strongly implicated intercellular communication through gap junctions and calcium release from intracellular stores as mediators of collective gradient sensing. The resulting integrative analysis provides a framework for understanding the advantages and limitations of sensory information processing by relays of chemically coupled cells.

Biophysics↗