Aug
12
Mon
2013
Invited Talk: Can we compute what we think? @ Amriteshwari Hall
Aug 12 @ 10:20 am – 10:51 am

gauteGaute Einevoll, Ph.D.
Professor of Physics, Department of Mathematical Sciences & Technology, Norwegian University of Life Sciences (UMB)


Multiscale modeling of cortical network activity: Key challenges

Gaute T. Einevoll Computational Neuroscience Group, Norwegian University of Life Sciences, 1432 Ås, Norway; Norwegian National Node of the International Neuroinformatics Coordinating Facility (INCF)

Several challenges must be met in the development of multiscale models of cortical network activity. In the presentation I will, based on ongoing work in our group (http://compneuro.umb.no/ ) on multiscale modeling of cortical columns, outline some of them. In particular,

  1. Combined modeling schemes for neuronal, glial and vascular dynamics [1,2],
  2. Development of sets of interconnected models describing system at different levels of biophysical detail [3-5],
  3. Multimodal modeling, i.e., how to model what you can measure [6-12],
  4. How to model when you don’t know all the parameters, and
  5. Development of neuroinformatics tools and routines to do simulations efficiently and accurately [13,14].

References:

  1. L. Øyehaug, I. Østby, C. Lloyd, S.W. Omholt, and G.T. Einevoll: Dependence of spontaneous neuronal firing and depolarisation block on astroglial membrane transport mechanisms, J Comput Neurosci 32, 147-165 (2012)
  2. I. Østby, L. Øyehaug, G.T. Einevoll, E. Nagelhus, E. Plahte, T. Zeuthen, C. Lloyd, O.P. Ottersen, and S.W. Omholt: Astrocytic mechanisms explaining neural-activity-induced shrinkage of extraneuronal space, PLoS Comp Biol 5, e1000272 (2009)
  3. T. Heiberg, B. Kriener, T. Tetzlaff, A. Casti, G.T. Einevoll, and H.E. Plesser: Firing-rate models can describe the dynamics of the retina-LGN connection, J Comput Neurosci (2013)
  4. T. Tetzlaff, M. Helias, G.T. Einevoll, and M. Diesmann: Decorrelation of neural-network activity by inhibitory feedback, PLoS Comp Biol 8, e10002596 (2012).
  5. E. Nordlie, T. Tetzlaff, and G.T. Einevoll: Rate dynamics of leaky integrate-and-fire neurons with strong synapses, Frontiers in Comput Neurosci 4, 149 (2010)
  6. G.T. Einevoll, F. Franke, E. Hagen, C. Pouzat, K.D. Harris: Towards reliable spike-train recording from thousands of neurons with multielectrodes, Current Opinion in Neurobiology 22, 11-17 (2012)
  7. H. Linden, T Tetzlaff, TC Potjans, KH Pettersen, S Grun, M Diesmann, GT Einevoll: Modeling the spatial reach of LFP, Neuron 72, 859-872 (2011).
  8. H. Linden, K.H. Pettersen, and G.T. Einevoll: Intrinsic dendritic filtering gives low-pass power spectra of local field potentials, J Computational Neurosci 29, 423-444 (2010)
  9. K.H. Pettersen and G.T. Einevoll: Amplitude variability and extracellular low-pass filtering of neuronal spikes, Biophysical Journal 94, 784-802 (2008).
  10. K.H. Pettersen, E. Hagen, and G.T. Einevoll: Estimation of population firing rates and current source densities from laminar electrode recordings, J Comput Neurosci 24, 291-313 (2008).
  11. K. Pettersen, A. Devor, I. Ulbert, A.M. Dale and G.T. Einevoll. Current-source density estimation based on inversion of electrostatic forward solution: Effects of finite extent of neuronal activity and conductivity discontinuities, Journal of Neuroscience Methods 154, 116-133 (2006).
  12. G.T. Einevoll, K. Pettersen, A. Devor, I. Ulbert, E. Halgren and A.M. Dale: Laminar Population Analysis: Estimating firing rates and evoked synaptic activity from multielectrode recordings in rat barrel cortex, Journal of Neurophysiology 97, 2174-2190 (2007).
  13. LFPy: A tool for simulation of extracellular potentials (http://compneuro.umb.no)
  14. E. Nordlie, M.-O. Gewaltig, H. E. Plesser: Towards reproducible descriptions of neuronal network models, PLoS Comp Biol 5, e1000456 (2009).

Gaute

Aug
13
Tue
2013
Plenary Talk: Biosensor and Single Cell Manipulation using Nanopipettes @ Amriteshwari Hall
Aug 13 @ 10:06 am – 10:49 am

NaderNader 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.

Delegate Talk: A Novel Versatile Human Cell Based In Vitro High Throughput Genotoxicity Screen @ Acharya Hall
Aug 13 @ 6:50 pm – 7:00 pm
Delegate Talk: A Novel Versatile Human Cell Based In Vitro High Throughput Genotoxicity Screen @ Acharya Hall | Vallikavu | Kerala | India

Sunilkumar Sukumaran, Ayyappan Nair, Madhuri Subbiah, Gunja Gupta, Lakshmi Rajakrishna, Pradeep Savanoor Raghavendra, Subbulakshmi Karthikeyan, Salini Krishnan Unni and Ganesh Sambasivam


Genotoxicity is defined as DNA damage that leads to gene mutations which can become tumorigenic. Genotoxicity testing is important to ensure drug safety and is mandatory prior to Phase I/II clinical trials of new drugs. The results from genetic toxicology studies help to identify hazardous drugs and environmental genotoxins. Currently, among others there are four tests recommended by regulatory authorities (Ames test-bacterial, chromosome aberrations; in vitro gene mutation-eukaryotic cells and in vivo test). These assays are laborious, time consuming, require large quantities of test compounds and limited by throughput challenges. The site and mechanism of genotoxicity are not revealed by these assays and data obtained from bacterial tests might not translate the same in mammals. To address these we have developed a novel, versatile, human cell based, high throughput, reporter based genotoxicity screen (Anthem’s Genotox screen). This screen is performed on genetically engineered human cell lines that express 3 reporter genes under transcriptional control of ‘early DNA damage sensors’ (p53, p21 and GADD153). These genes are involved in DNA repair, cell cycle arrest and/or apoptosis. p21 and GADD are also known to be induced in a p53 independent manner. p53 blocks G1/S transition of cell cycle while the p53 independent DNA damage block G2/M transition. Identification of the mechanism of genotoxicity helps in rational drug designing. Additionally, the platform can be used to screen other potential genotoxins from cosmetics, food and environment. Initial validation studies of the Genotox screen was performed with over 60 compounds chosen from a variety of chemical classes. The genotoxic potential of metabolites was tested using rat liver S9 fractions. The results demonstrated a sensitivity of 86.7–92.3% and a specificity of 70–78.6% when compared with currently available in vitro genotoxicity assays. This Genotox screen would prove to be an invaluable human cell based tool to weed out potential genotoxins in various industries.

Aug
14
Wed
2013
Invited Talk: A draft map of the human proteome @ Amriteshwari Hall
Aug 14 @ 10:42 am – 11:30 am

akhileshAkhilesh 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.

Akhilesh (2)