Aug
12
Mon
2013
Invited Talk: Neuroprotective and neurodestructive effects of Ayurvedic drug constituents: Parkinson’s disease @ Amriteshwari Hall
Aug 12 @ 2:55 pm – 3:20 pm

mohanakumarK. P. Mohanakumar, Ph.D.
Chief Scientist, Cell Biology & Physiology Division, Indian Institute of Chemical Biology, Kolkata


Neuroprotective and neurodestructive effects of Ayurvedic drug constituents: Parkinson’s disease

The present study reports the good and the bad entities in an Indian traditional medicine used for treating Parkinson’s disease (PD). A prospective clinical trial on the effectiveness of Ayurvedic medication in a population of PD patients revealed significant benefits, which has been attributed to L-DOPA present in the herbs [1]. Later studies revealed better benefits with one of the herbs alone, compared to pure L-DOPA in a clinical trial conducted in UK [2], and in several studies conducted on animal models of PD in independent laboratories world over [3-5]. We have adapted strategies to segregate molecules from the herb, and then carefully removed L-DOPA contained therein, and tested each of these sub-fractions for anti-PD activity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, rotenone and 6-hydroxydopamine -induced parkinsonian animal models, and transgenic mitochondrial cybrids. We report here two classes of molecules contained in the herb, one of which possessed severe pro-parkinsonian (phenolic amine derivatives) and the other having excellent anti-parkinsonian potential (substituted tetrahydroisoquinoline derivatives). The former has been shown to cause severe dopamine depletion in the striatum of rodents, when administered acutely or chronically. It also caused significant behavioral aberrations, leading to anxiety and depression [6]. The latter class of molecules administered in PD animal model [7], caused reversal of behavioral dysfunctions and significant attenuation of striatal dopamine loss. These effects were comparable or better than the effects of the anti-PD drugs, selegiline or L-DOPA. The mechanism of action of the molecule has been found to be novel, at the postsynaptic receptor signaling level, as well as cellular α-synuclein oligomerization and specifically at mitochondria. The molecule helped in maintaining mitochondrial ETC complex activity and stabilized cellular respiration, and mitochondrial fusion-fission machinery with specific effect on the dynamin related protein 1. Although there existed significant medical benefits that could be derived to patients due to the synergistic actions of several molecules present in a traditional preparation, accumulated data in our hands suggest complicated mechanisms of actions of Ayurvedic medication. Our results also provide great hope for extracting, synthesizing and optimizing the activity of anti-parkinsonian molecules present in traditional Ayurvedic herbs, and for designing novel drugs with novel mechanisms of action.

  1. N, Nagashayana, P Sankarankutty, MRV Nampoothiri, PK Mohan and KP Mohanakumar, J Neurol Sci. 176, 124-7, 2000.
  2. Katzenschlager R, Evans A, Manson A, Patsalos PN, Ratnaraj N, Watt H, Timmermann L, Van der Giessen R, Lees AJ. J Neurol Neurosurg Psychiatry.75, 1672-7, 2004.
  3. Manyam BV, Dhanasekaran M, Hare TA. Phytother Res. 18, 706-12, 2004.
  4. Kasture S, Pontis S, Pinna A, Schintu N, Spina L, Longoni R, Simola N, Ballero M, Morelli M. Neurotox Res. 15, 111-22, 2009.
  5. Lieu CA, Kunselman AR, Manyam BV, Venkiteswaran K, Subramanian T. Parkinsonism Relat Disord.16, 458-65, 2010.
  6. T Sengupta and KP Mohanakumar, Neurochem Int. 57, 637-46, 2010.
  7. T Sengupta, J Vinayagam, N Nagashayana, B Gowda, P Jaisankar and KP Mohanakumar, Neurochem Res 36, 177-86, 2011

MOhan (1) MOhan (2)

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.

Plenary Talk: Interspike Interval Distribution of Neuronal Model with distributed delay: Emergence of unimodal, bimodal and Power law @ Sathyam Hall
Aug 13 @ 1:20 pm – 2:00 pm

karmeshuKarmeshu, Ph.D.
Dean & Professor, School of Computer & Systems Sciences & School of Computational & Integrative Sciences, Jawaharlal Nehru University, India.


Interspike Interval Distribution of Neuronal Model with distributed delay: Emergence of unimodal, bimodal and Power law

The study of interspike interval distribution of spiking neurons is a key issue in the field of computational neuroscience. A wide range of spiking patterns display unimodal, bimodal  ISI patterns including power law behavior. A challenging problem is to understand the biophysical mechanism which can generate  the empirically observed patterns. A neuronal model with distributed delay (NMDD) is proposed and is formulated as an integro-stochastic differential equation which corresponds to a non-markovian process. The widely studied IF and LIF models become special cases of this model. The NMDD brings out some interesting features when excitatory rates are close to inhibitory  rates rendering the drift close to zero. It is interesting that NMDD model with gamma type memory kernel can also account for bimodal ISI pattern. The mean delay of the memory kernels plays a significant role in bringing out the transition from unimodal to bimodal  ISI distribution. It is interesting to note that when a collection of neurons group together and fire together, the ISI distribution exhibits  power law.

 

Invited Talk: From Camels to Worms: Novel Approaches for Drug Discovery in Parkinson’s Disease. @ Acharya Hall
Aug 13 @ 3:02 pm – 3:23 pm

TimGuilliamsTim Guilliams, Ph.D.
Junior Associate Fellow at the Centre for Science and Policy, University of Cambridge


From Camels to Worms: Novel Approaches for Drug Discovery in Parkinson’s Disease

The discovery of novel treatments for neurodegenerative diseases, such as Parkinson’s disease, represents one of the biggest scientific challenges of the 21st century. The development of new tools and models to study the mechanisms underlying neurotoxicity is therefore essential. During my talk, I will outline new strategies for drug design and innovation used during my PhD at the University of Cambridge, which include the combination of fluorescent nematode worms, camelid antibody fragment technology and chemical compounds. These novel approaches will help us to gain insights into the key pathogenic steps involved in Parkinson’s disease and potentially lead to new therapeutic strategies.

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)