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.

Invited Talk: Nanomaterials for ‘enzyme-free’ biosensing @ Amriteshwari Hall
Aug 13 @ 2:17 pm – 2:35 pm

SatheeshSatheesh 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.

Satheesh

Invited Talk: The system of PAS proteins (HIF and AhR) as an interface between environment and skin homeostasis @ Acharya Hall
Aug 13 @ 2:33 pm – 2:50 pm

andreyAndrey Panteleyev, Ph.D.
Vice Chair, Division of Molecular Biology, NBICS Centre-Kurchatov Institute, Moscow, Russia


The system of PAS proteins (HIF and AhR) as an interface between environment and skin homeostasis

Regulation of normal skin functions as well as etiology of many skin diseases are both tightly linked to the environmental impact. Nevertheless, molecular aspects of skin-environment communication and mechanisms coordinating skin response to a plurality of environmental stressors remain poorly understood.

Our studies along with the work of other groups have identified the family of PAS dimeric transcription factors as an essential sensory and regulatory component of communication between skin and the environment. This protein family comprises a number of hypoxia-induced factors (HIF-alpha proteins), aryl hydrocarbon receptor (AhR), AhR nuclear translocator (ARNT), and several proteins implicated in control of rhythmic processes (Clock, Period, and Bmal proteins). Together, various PAS proteins (and first of all ARNT – as the central dimerization partner in the family) control such pivotal aspects of cell physiology as drug/xenobiotic metabolism, hypoxic and UV light response, ROS activity, pathogen defense, overall energy balance and breathing pathways.

In his presentation Dr. Panteleyev will focus on the role of ARNT activity and local hypoxia in control of keratinocyte differentiation and cornification. His recent work revealed that ARNT negatively regulates expression of late differentiation genes through modulation of amphiregulin expression and downstream alterations in activity of EGFR pathway. All these effects are highly dependent on epigenetic mechanisms such as histone deacetylation. Characterisation of hypoxia as a key microenvironmental factor in the skin and the role of HIF pathway in control of dermal vasculature and epidermal functions is another major focus of Dr. Panteleyev’s presentation.

In general, the studies of Dr. Panteleyev’s laboratory provide an insight into the PAS-dependent maintenance of skin homeostasis and point to the potential role of these proteins in pathogenesis of environmentally-modulated skin diseases such as barrier defects, desquamation abnormalities, psoriasis, etc.

 

Delegate Talk: Novel Cell-Based Biosensors for High Throughput Toxin Detection and Drug Screening Applications @ Amriteshwari Hall
Aug 13 @ 4:08 pm – 4:23 pm
Delegate Talk:  Novel Cell-Based Biosensors for High Throughput Toxin Detection and Drug Screening Applications @ Amriteshwari Hall | Vallikavu | Kerala | India

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)