Quarterly e -Newsletter from Bioinformatics Centre (DIC) Volume III, Issue III Kerala Agricultural University, Thrissur. September 2011 About Us

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1 Biobits Quarterly e -Newsletter from Bioinformatics Centre (DIC) Kerala Agricultural University, Thrissur. Volume III, Issue III September 2011 About Us The Bioinformatics Centre (DIC) at KAU runs under the Biotechnology Information System Network (BTISnet) programme of DBT, Ministry of Science & Technology, and Government of India. The Centre was upgraded to Distributed Information Centre during 2004 to promote Bioinformatics research and education. The Centre enhances access to global information in life sciences especially plant sciences and plant biotechnology involving scientists and students of the University and other S&T institutions and acts as a support centre to the Centre for Plant Biotechnology & Molecular Biology. The Centre is involved in a wide range of research work on plant responses to biotic and abiotic stresses, plant metabolomics using systems biology approaches, plant-pathogen interaction studies and study of active compounds in anti cancer medicinal plants. In addition to this, the Centre offers a credit course in Bioinformatics to post graduate Plant Biotechnology students, conducts training programmes in Bioinformatics and maintains various databases relevant to agriculture. This e-newsletter is a venture from our centre Cover Story Proteomics & Genomics Drug Discovery Agricultural Bioinformatics News Archive Our Focus Cutting Edge Discovery Today Letters & Ideas Cover Story Bioinformatics is not only the hub of all life sciences it is also cutting edge knowledge for those who would like to make a breakthrough Advances in bioinformatics offer unprecedented opportunities for biologists to rapidly collect and analyze enormous amounts of data. These vast stores of information have a rich potential to expedite scientific discovery and prevent expensive duplication of experiments In fields ranging from structural biology to genomics, ready access to data, analytical and computational tools are fundamentally changing the way life science investigators conduct research and approach problems... Complex computationally intensive biological problems are now being addressed and promise to significantly advance our understanding of biology No biological discipline will be unaffected by these technological breakthroughs. Bioinformatics can revolutionize not only the research sector but its judicious application can do wonders in transferring knowledge to millions of marginal farmers of the country

2 Proteomics & Genomics Jumping Genes Caught in the Act: New Evidence That the Genome Contains Many Mobile Elements An ambitious hunt for actively "jumping genes" in humans has yielded compelling new evidence that the genome, anything but static, contains numerous pesky mobile elements that may help to explain why people have such a variety of physical traits and disease risks. Bioinformatics is used to compare the standard assembly of genetic elements as outlined in the reference human genome to raw whole-genome data from 310 individuals recently made available by the 1000 Genomes Project, the team revealed 1,016 new insertions of RIPs, or retrotransposon insertion polymorphisms, thereby expanding the catalog of insertions that are present in some individuals and absent in others. Retrotransposons are travelling bits of DNA that replicate by copying and pasting themselves at new locations in the genome. Having duplicated themselves and accumulated over evolutionary history, transposable elements now make up about half of the human genome. Drug Discovery Curcumin Compound Improves Effectiveness of Head and Neck Cancer Treatment A primary reason that head and neck cancer treatments fail is the tumor cells become resistant to chemotherapy drugs. Recent studies have found that a compound derived from the Indian spice curcumin can help cells overcome that resistance. So adding a curcumin-based compound, called FLLL32, to head and neck cancer cell lines, helped to cut the dose of the chemotherapy drug cisplatin by four while still killing tumor cells equally as well as the higher dose of cisplatin without FLLL32. This work opens the possibility of using lower, less toxic doses of cisplatin to achieve an equivalent or enhanced tumor kill. Typically, when cells become resistant to cisplatin, we have to give increasingly higher doses.

3 FLLL32 is designed to sensitize cancer cells at a molecular level to the antitumor effects of cisplatin. It targets a key type of protein called STAT3 that is seen at high levels in about 82 percent of head and neck cancers. High levels of STAT3 are linked to problems with normal cell death processes, which allow cancer cells to survive chemotherapy treatment. STAT3 activation has been associated with cisplatin resistance in head and neck cancer. Curcumin is known to inhibit STAT3 function, but it is not well-absorbed by the body. In the current study, researchers compared varying doses of cisplatin alone with varying doses of cisplatin plus FLLL32 against two sets of head and neck cancer cells: one line that was sensitive to cisplatin and one line that was resistant. They found that FLLL32 decreased the activation levels of STAT3, sensitizing both resistant and sensitive tumor cells to cisplatin. Further, lower doses of cisplatin with FLLL32 were equally effective at killing cancer cells as the higher doses of cisplatin alone. Separate studies suggest FLLL32 may not be wellabsorbed by the body and researchers are developing a next generation compound that they hope improves on that. Agricultural Bioinformatics Work With RNA Silencing and Plant Stem Cells May Lead to Controlling Fruit, Seed and Leaves Research on controlling the stem cells of plants could eventually lead to learning how to make them produce more fruit, seed and leaves. Working with the shoot meristem area, we may (eventually) control fruit and seed yield or plant mass by manipulating the development and maintenance of plant stem cells. In plants, the shoot meristem area is composed of undifferentiated cells, which means they can be programmed by the plant to become various structures - leaf, stem, branches flower, etc. The team worked with Arabidopsis, a plant also known as rock cress, which is related to cabbage and mustard. Arabidopsis is often used for studying plant biology because it is the first plant to have its entire genome sequenced.

4 Previous studies had shown that the Arabidopsis gene known as argonaute 10, or simply AGO10, plays a critical role in regulating meristem cell development. Arabidopsis has 10 AGO genes, and it was known that AGO10 is involved in various biological processes such as merited development and proper leaf formation. Although the genetic functions of AGO10 have been described, the molecular mechanism by which it regulates SAM (shoot apical meristem) development remained unknown. Though composed of only a few bases, micrornas often perform a critical function by switching the expression of certain genes off. Turning off gene expression is just as important a regulatory mechanism in plant development as switching genes on. The team proposed that AGO10 functions as "a decoy for mir166/165 to prevent it being loaded into other AGO proteins, particularly AGO1, which" plays a potent but inhibitory role in correct development of the meristem area cells. But if mir166/165 is loaded into AGO10 protein, they will not switch-off target genes. Thus, AGO10 works in an opposite way compared to AGO1: It protects target genes and secures their expression. News Archive Biological 'Computer' Destroys Cancer Cells: Diagnostic Network Incorporated Into Human Cells This network recognizes certain cancer cells using logic combinations of five cancer-specific molecular factors, triggering cancer cells destruction. Researcher s goal is to construct biocomputers that detect molecules carrying important information about cell wellbeing and process this information to direct appropriate therapeutic response if the cell is found to be abnormal. Previous studies described that a multi-gene synthetic "circuit" task is to distinguish between cancer and healthy cells and subsequently target cancer cells for destruction.

5 This circuit works by sampling and integrating five intracellular cancer-specific molecular factors and their concentration. The circuit makes a positive identification only when all factors are present in the cell, resulting in highly precise cancer detection. The gene network was tested in two types of cultured human cells: cervical cancer cells, called HeLa cells, and normal cells. When the genetic bio-computer was introduced into the different cell types, only HeLa cells, but not the healthy ones, were destroyed. In the human body there are about 250 different healthy cell types. In addition, there are numerous variants of cancer cells, of which hundreds can be grown in the laboratory. Still greater is the diversity of mirna: between 500 to 1000 different species have been described in human cells. Our Focus Computational Assay of Phytochemicals in Rauwolfia serpentina and its effects on protein Dardarin Rauwolfia serpentina which is also known as Rauwolfia or Indian Snakeroot in traditional medicine system has been used for treating snake bite. This herb is highly effective in the treatment of high blood pressure. It contains a number of bioactive chemicals which are mostly alkaloids which shows highly complex pattern of action. Extracts from the plant is conventionally used to cure various neurological ailments, insanity, mental illness and traumas. Modeled structure of LRRK2 Leucine-rich repeat kinase 2 (LRRK2), also known as dardarin, is an enzyme that in humans is encoded by the LRRK2 gene. Variants of this gene are associated with an increased risk of Parkinson's disease and also Crohn's disease.

6 The frequency of LRRK2 mutations in a series of 118 cases of familial Parkinson s disease is 5.1%. The study was carried out to identify a phytochemical from Rauwolfia serpentina which can interact with protein dardarin and which may be lead into a potential drug for neurogenetic diseases. The alkaloid episarpagine from the plant which is found to have interaction with the protein may act as a potential drug against several neuro degenerative disorders. Cutting Edge Protein Folding Made Easy Protein folding is one of the central questions in biochemistry. Protein folding is the continual and universal process whereby the long, coiled strings of amino acids that make up proteins in all living things fold into more complex three-dimensional structures. By understanding how proteins fold, a researcher is able to move closer to predicting their function. This is important because incorrectly folded proteins in humans result in such devastating diseases as Alzheimer's, Parkinson's, Huntington's, emphysema and cystic fibrosis. Developing better modeling techniques for protein folding is crucial to creating more effective pharmaceutical treatments for these and other diseases. Computational methods of modeling protein folding have existed for a couple of decades. A new algorithm has been developed to examine a protein's fundamental chemical properties and then to scan a number of possible protein shapes before predicting the final form that the protein is likely to take. The results by this method were truly impressive. Whereas classical techniques for predicting protein folding pathways required hundreds of thousands of CPU hours to compute the folding dynamics of 40 amino acids proteins, this new method enable to predict correctly in 10 minutes on a single laptop, a coarse-grained representation of the folding pathways of a protein with 60 amino acids.

7 Discovery Today Naturally Occurring Plant Alkaloids Could Slow Down Alzheimer's Disease A family of naturally occurring plant compounds could help prevent or delay memory loss associated with Alzheimer's disease. Beta-carboline alkaloids could potentially be used in therapeutic drugs to stop, or at least slow down, the progressively debilitating effects of Alzheimer's. One of these alkaloids, called harmine, inhibits a protein known as DYRK1A, which has been implicated by this and other studies in the formation tau phosphorylation. This process dismantles the connections between brain cells, or neurons, and has been linked in past TGen studies to Alzheimer's disease. Tau is a protein critical to the formation of the microtubule bridges in neurons. These bridges support the synaptic connections that, like computer circuits, allow brain cells to communicate with each other. Pharmacological inhibition of DYRK1A through the use of beta-carboline alkaloids may provide an opportunity to intervene therapeutically to alter the onset or progression of tau pathology in Alzheimer's disease. Beta-carboline alkaloids are natural occurring compounds in some medicinal plant species that affect multiple central nervous system targets. They have antioxidant properties, and have been shown to protect brain cells from excessive stimulation of neurotransmitters. This process of tau phosphorylation enables connections between brain cells to unbind and bind again, allowing neurons to connect and reconnect with other brain cells. However, this process can go awry, allowing the formation of neurofibrillary tangles, one of the signature indicators of Alzheimer's. Laboratory tests showed that harmine, and several other beta-carboline alkaloids, "potently reduced'' the expression of three forms of phosphorylated tau, and inhibited the ability of DYRK1A to phosphorylate tau protein at multiple genetic sites associated with tau pathology. These results suggest that this class of compounds warrant further investigation as candidate tau-based therapeutics to alter the onset or progression of tau dysfunction and pathology in Alzheimer's disease.

8 Letters & Ideas This particular column is especially for readers those who would like to share and suggest ideas and comments. Please mail to or Training A 21 days Winter School on Advances in Micropropagation of Horticulture Crops is being conducted at the Centre for Plant Biotechnology and Molecular Biology, Kerala Agricultural University, Vellanikkara, Thrissur for 25 participants from December 1-21, For more details visit our website: How to Reach Us About The Team: Dr.R.Keshavachandran (Coordinator) Sreejisha P.S, Natalia Aniyankunju, Emma Jose Bioinformatics Centre (DIC), ITBT Complex, Kerala Agricultural University, KAU P.O, Thrissur, Kerala kaubioinfo@gmail.com, kauniv.btisnet@nic.in or bic@kau.in Ph: , Fax: Click here for our BioBits Archive