Rohit Manchanda, Ph.D.
Professor, Biomedical Engineering Group, IIT-Bombay, India
Modelling the syncytial organization and neural control of smooth muscle: insights into autonomic physiology and pharmacology
We have been studying computationally the syncytial organization and neural control of smooth muscle in order to help explain certain puzzling findings thrown up by experimental work. This relates in particular to electrical signals generated in smooth muscles, such as synaptic potentials and spikes, and how these are explicable only if three-dimensional syncytial biophysics are taken fully into account. In this talk, I shall provide an illustration of outcomes and insights gleaned from such an approach. I shall first describe our work on the mammalian vas deferens, in which an analysis of the effects of syncytial coupling led us to conclude that the experimental effects of a presumptive gap junction uncoupler, heptanol, on synaptic potentials were incompatible with gap junctional block and could best be explained by a heptanol-induced inhibition of neurotransmitter release, thus compelling a reinterpretation of the mechanism of action of this agent. I shall outline the various lines of evidence, based on indices of syncytial function, that we adduced in order to reach this conclusion. We have now moved on to our current focus on urinary bladder biophysics, where the questions we aim to address are to do with mechanisms of spike generation. Smooth muscle cells in the bladder exhibit spontaneous spiking and spikes occur in a variety of distinct shapes, making their generation problematic to explain. We believe that the variety in shapes may owe less to intrinsic differences in spike mechanism (i.e., in the complement of ion channels participating in spike production) and more to features imposed by syncytial biophysics. We focus especially on the modulation of spike shape in a 3-D coupled network by such factors as innervation pattern, propagation in a syncytium, electrically finite bundles within and between which the spikes spread, and some degree of pacemaker activity by a sub-population of the cells. I shall report two streams of work that we have done, and the tentative conclusions these have enabled us to reach: (a) using the NEURON environment, to construct the smooth muscle syncytium and endow it with synaptic drive, and (b) using signal-processing approaches, towards sorting and classifying the experimentally recorded spikes.
Colin Barrow, Ph.D.
Chair in Biotechnology, School of Life & Environmental Sciences, Deakin University, Australia
Nano-biotechnology: Omega-3 Oils and Nanofibres
The health benefits of long-chain omega-3 fatty acids are well established, especially for eicosapentaenoic acid (EPA) and docosapentaenoic acid (DHA) from fish and microbial sources. In fact, a billion dollar market exists for these compounds as nutritional supplements, functional foods and pharmaceuticals. This presentation will describe some aspects of our omega-3 biotechnology research that are at the intersection of Nano-biotechnology and oil chemistry. These include the use of lipases for the concentration of omega-3 fats, through immobilization of these lipases on nanoparticles, and the microencapsulation and stabilization of omega-3 oils for functional foods. I will also describe some of our work on the enzymatic production of resolvins using lipoxygenases, and the fermentation of omega-3 oils from marine micro-organisms. Finally, I will describe some of our work on the formation of amyloid fibrils and graphene for various applications in nano-biotechnology.
David Ibanez, Laura Dubreuil and Alejandro Rier
Neurofeedback (NF) is a type of biofeedback that uses real time display of electroencephalography to illustrate brain activity. EEG features are extracted and displayed allowing the user to, with practice, modulate their temporal evolution. Neurofeedback training has many therapeutic applications such as attention deficit hyperactivity disorder (ADHD), migraine, depression or conduct disorders. This document presents NeuroSurfer, a novel general-purpose tool for neurofeedback training with a use case of attention deficit hyperactivity disorder (ADHD) treatment.
Suryaprakash Sambhara, DVM, Ph.D
Chief, Immunology Section, Influenza Division, CDC, Atlanta, USA
Making sense of pathogen sensors of Innate Immunity: Utility of their ligands as antiviral agents and adjuvants for vaccines.
Currently used antiviral agents act by inhibiting viral entry, replication, or release of viral progeny. However, recent emergence of drug-resistant viruses has become a major public health concern as it is limiting our ability to prevent and treat viral diseases. Furthermore, very few antiviral agents with novel modes of action are currently in development. It is well established that the innate immune system is the first line of defense against invading pathogens. The recognition of diverse pathogen-associated molecular patterns (PAMPs) is accomplished by several classes of pattern recognition receptors (PRRs) and the ligand/receptor interactions trigger an effective innate antiviral response. In the past several years, remarkable progress has been made towards understanding both the structural and functional nature of PAMPs and PRRs. As a result of their indispensable role in virus infection, these ligands have become potential pharmacological agents against viral infections. Since their pathways of action are evolutionarily conserved, the likelihood of viruses developing resistance to PRR activation is diminished. I will discuss the recent developments investigating the potential utility of the ligands of innate immune receptors as antiviral agents and molecular adjuvants for vaccines.
Nader Pourmand, Ph.D.
Director, UCSC Genome Technology Center,University of California, Santa Cruz
Biosensor and Single Cell Manipulation using Nanopipettes
Approaching sub-cellular biological problems from an engineering perspective begs for the incorporation of electronic readouts. With their high sensitivity and low invasiveness, nanotechnology-based tools hold great promise for biochemical sensing and single-cell manipulation. During my talk I will discuss the incorporation of electrical measurements into nanopipette technology and present results showing the rapid and reversible response of these subcellular sensors to different analytes such as antigens, ions and carbohydrates. In addition, I will present the development of a single-cell manipulation platform that uses a nanopipette in a scanning ion-conductive microscopy technique. We use this newly developed technology to position the nanopipette with nanoscale precision, and to inject and/or aspirate a minute amount of material to and from individual cells or organelle without comprising cell viability. Furthermore, if time permits, I will show our strategy for a new, single-cell DNA/ RNA sequencing technology that will potentially use nanopipette technology to analyze the minute amount of aspirated cellular material.
Sharmila Mande, Ph.D.
Principal Scientist and Head, Bio Sciences R&D, TCS Innovation Labs, Pune
Gut microbiome and health: Moving towards the new era of translational medicine
The microbes inhabiting our body outnumber our own cells by a factor of 10. The genomes of these microbes, called the ‘second genome’ are therefore expected to have great influence on our health and well being. The emerging field of metagenomics is rapidly becoming the method of choice for studying the microbial community (called microbiomes) present in various parts of the human body. Recent studies have implicated the role of gut microbiomes in several diseases and disorders. Studies have indicated gut microbiome’s role in nutrient absorption, immuno-modulation motor-response, and other key physiological processes. However, our understanding of the role of gut microbiota in malnutrition is currently incomplete. Exploration of these aspects are likely to help in understanding the microbial basis for several physiological disorders associated with malnutrition (eg, increased susceptibility to diarrhoeal pathogens) and may finally aid in devising appropriate probiotic strategies addressing this menace. A metagenomic approach was employed for analysing the differences between gut microbial communities obtained from malnourished and healthy children. Results of the analysis using TCS’ ‘Metagenomic Analysis Platform’ were discussed in detail during my talk.
Satheesh Babu T. G., Ph.D.
Associate Professor, Department of Sciences, School of Engineering, Amrita University, Coimbatore, India
Nanomaterials for ‘enzyme-free’ biosensing
Enzyme based sensors have many draw backs such as poor storage stability, easily affected by the change in pH and temperature and involves complicated enzyme immobilization procedures. To address this limitation, an alternative approach without the use of enzyme, “non-enzymatic” has been tried recently. Choosing the right catalyst for direct electrochemical oxidation / reduction of a target molecule is the key step in the fabrication of non-enzymatic sensors.
Non-enzymatic sensors for glucose, creatinine, vitamins and cholesterol are fabricated using different nanomaterials, such as nanotubes, nanowires and nanoparticles of copper oxide, titanium dioxide, tantalum oxide, platinum, gold and graphenes. These sensors selectively catalyse the targeted analyte with very high sensitivity. These nanomaterials based sensors combat the drawbacks of enzymatic sensors.
Anupama Natarajan, James Hickman and Peter Molnar
Novel Cell-Based Biosensors for High Throughput Toxin Detection and Drug Screening Applications
Over the last decade there has been focus on the development of cellbased biosensors to detect environmental toxins or to combat the threats of biological warfare. These sensors have been shown to have multiple applications including understanding function and behaviour at the cellular and tissue levels, in cell electrophysiology and as drug screening tools that can eliminate animal testing. These factors make the development of cell-based biosensors into high throughput systems a priority in pharmacological, environmental and defence industries (Pancrazio J J et al. 1999, Kang G et al. 2009, Krinke D et al. 2009). We have developed a high through-put in vitro cell-silicon hybrid platform that could be used to analyze both cell function and response to various toxins and drugs. Our hypothesis was that by utilizing surface modification to provide external guidance cues as well as optimal growth conditions for different cell types (Cardiac and Neuronal), we could enhance the information output and content of such a system. An intrinsic part of this study was to create ordered or patterned functional networks of cells on Micro-electrode arrays (MEA). Such engineered networks had a two-fold purpose in that they not only aided in a more accurate analysis of cell response and cell and tissue behaviour, but also increased the efficiency of the system by increasing the connectivity and placement of the cells over the recording electrodes. Here we show the response of this system to various toxins and drugs and the measurement of several vital cardiac parameters like conduction velocity and refractory period (Natarajan A et al. 2011)
Akhilesh Pandey, Ph.D.
Professor, Johns Hopkins University School of Medicine, Baltimore, USA
A draft map of the human proteome
We have generated a draft map of the human proteome through a systematic and comprehensive analysis of normal human adult tissues, fetal tissues and hematopoietic cells as an India-US initiative. This unique dataset was generated from 30 histologically normal adult tissues, fetal tissues and purified primary hematopoietic cells that were analyzed at high resolution in the MS mode and by HCD fragmentation in the MS/MS mode on LTQ-Orbitrap Velos/Elite mass spectrometers. This dataset was searched against a 6-frame translation of the human genome and RNA-Seq transcripts in addition to standard protein databases. In addition to confirming a large majority (>16,000) of the annotated protein-coding genes in humans, we obtained novel information at multiple levels: novel protein-coding genes, unannotated exons, novel splice sites, proof of translation of pseudogenes (i.e. genes incorrectly annotated as pseudogenes), fused genes, SNPs encoded in proteins and novel N-termini to name a few. Many proteins identified in this study were identified by proteomic methods for the first time (e.g. hypothetical proteins or proteins annotated based solely on their chromosomal location). We have generated a catalog of proteins that show a more tissue-restricted pattern of expression, which should serve as the basis for pursuing biomarkers for diseases pertaining to specific organs. This study also provides one of the largest sets of proteotypic peptides for use in developing MRM assays for human proteins. Identification of several novel protein-coding regions in the human genome underscores the importance of systematic characterization of the human proteome and accurate annotation of protein-coding genes. This comprehensive dataset will complement other global HUPO initiatives using antibody-based as well as MRM mass spectrometry-based strategies. Finally, we believe that this dataset will become a reference set for use as a spectral library as well as for interesting interrogations pertaining to biomedical as well as bioinformatics questions.
