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BioBits Volume VII Issue III September 2015 Quarterly E -Newsletter from Bioinformatics Centre (Dic) Kerala Agricultural University, Thrissur 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, plantpathogen 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 routine training programmes in Bioinformatics and maintains various databases relevant to agriculture. Cover Story Bioinformatics is not only the hub of all life sciences but also the cutting edge knowledge for those who would like to make a breakthrough… Bioinformatics and computational biology involve the use Plant Bioinformatics techniques informatics, statistics, biochemistry to solve including computer biological applied science, problems mathematics, chemistry usually and on sequence alignment, gene finding, genome assembly, protein structure alignment, protein structure prediction, prediction of gene expression and protein-ligand interactions etc. Complex computational and biological problems are now being addressed and this has led to significant advances in our understanding of biology. No biological discipline will be by these technological breakthroughs. Bioinformatics can revolutionize not only the research sector but its judicious application can do wonders in transferring Proteomics & Genomics News Archive Discovery Today Cutting Edge Our Focus Letters and Ideas the molecular level. Major research efforts in the field include unaffected Cover Story of knowledge to millions of marginal farmers of the country. This issue of ‘Biobits’ present before you the recent, most relevant developments/Research outcomes in Plant Biotechnology/ Bioinformatics. Plant Bioinformatics Contents How opium poppies synthesize morphine? Many people who live in developing countries do not have access to the pain relief that comes from morphine or other analgesics. That's because opiates are primarily derived from the opium poppy plant (Papaver somniferum) and are dependent on the plant health and supply around the world. After years of leading research on the opium poppy, scientists at the University of Calgary, Canada have characterized a novel gene that encodes the gateway enzyme in the formation of morphine - which describes how poppies synthesize the pain killing enzymes. The discovery opens the door to alternative production systems, aside from the plant itself. The gene they isolated actually consists of a natural fusion between two ancestral genes, which encodes the gateway enzyme in the formation of morphine. It's really interesting to see these fused genes in a metabolic pathway as it provides with a new tool to search for something missing in other plants as well. The findings were published in Nature Chemical Biology (2015), and detail the missing step to morphine biosynthesis. The gateway to morphine biosynthesis in opium poppy is the stereochemical inversion of (S)-reticuline since the enzyme Opium poppy plants where the biosynthesis of morphine occurs. enzyme yielding the first committed intermediate salutaridine is specific for (R)-reticuline. A fusion between a cytochrome P450 (CYP) and an aldo-keto reductase (AKR) catalyzes the S-to-R epimerization of reticuline via 1, 2-dehydroreticuline. The reticuline epimerase (REPI) fusion was detected in opium poppy. The researchers said that the isolation of this gene, among many other things, is a key step toward the reassembly of the pathway to morphine in microorganisms such as yeast. These efforts could lead to the development of alternative production systems for painkillers such as morphine, codeine and oxycodone. Source: http://www.sciencedaily.com/releases/2015/07/150713143657.htm Proteomics & Genomics Contents Oskar protein's structure revealed The structure of two parts of the Oskar protein, known to be essential for the development of reproductive cells, solved by scientists of EMBL Heidelberg was recently published in Cell Reports (2015). The research was carried out with fruit flies, but has implications for other animals, as many organisms, including humans, also have part of the Oskar protein. The Oskar protein which has a genetic role is essential for development process. Embryos that develop from fruit fly eggs lacking the normal amount of Oskar protein are unable to form germ cells - cells that allow reproduction - and so the resulting flies are sterile. Complete lack of the Oskar protein also prevents the embryo's abdomen from forming normally which limits its growth leading to death. In a healthy egg, Oskar initiates the formation of what's known as the germ plasm - a gathering of proteins Illustration of Oskar and its interactions with RNA and the Vasa helicase. and RNAs within the cytoplasm, which then goes on to form a new germ cell. Germ plasm normally forms in a particular position within the egg, but if Oskar is artificially moved elsewhere, the germ plasm will form in the new location. The co-author of the work has stated that solving the structure has enabled them to see how the different parts of the protein function at a molecular level, which could help us to understand more about this stage of development in a wide range of organisms. Using X-ray crystallography, the team was able to determine for the first time the structure of Oskar's two domains, called OSK and LOTUS. The OSK domain is found in some insects, including the fruit fly and the mosquito. The LOTUS domain is more widespread, being found in bacteria, plants and animals, including mice and in humans. They also found that only the OSK domain binds to RNA, specifically three RNAs derived from genes known to be important to germline development. The LOTUS domain did not bind to RNA; instead, the team found that LOTUS binds to Vasa helicase, an RNA binding protein with an RNA dependent helicase which is also one of the essential initial ingredients of the germ plasm. Vas, like LOTUS, is widely found in other organisms, including animals. The authors have said that there is still much to learn about how the Oskar protein functions and this work has opened up lots of exciting new avenues for investigation. Source: http://www.sciencedaily.com/releases/2015/07/150716135227.htm News Archive Contents Gene 'switch' reverses cancer in common childhood leukemia Melbourne researchers have shown that a type of leukemia can be successfully 'reversed' by coaxing the cancer cells back into normal development. Researchers from the Walter and Eliza Hall Institute showed that switching off a gene called Pax5 could cause cancer in a model of BALL, while restoring its function could 'cure' the disease. The discovery was made using a model of B-progenitor acute lymphoblastic leukemia (B-ALL), the most common cancer affecting children and the study was published in the journal Genes & Development (2015). The researchers stated that along with other genetic changes, deactivating Pax5 drives normal blood cells to turn into leukemia cells and they showed for the first time that reactivating Pax5 enabled the cells to resume their normal development and lose their cancer-like qualities, effectively curing the leukemia. One of the researchers said Pax5 was a gene frequently 'lost' in childhood B-ALL. Pax5 is essential for normal development of a type of white blood cells called B cells. From left to right, a red blood cell, a platelet and a white blood cell are shown. When Pax5 function is compromised, developing B cells can get trapped in an immature state and become cancerous. They have shown that restoring Pax5 function, even in cells that have already become cancerous, removes this 'block', and enables the cells to develop into normal white blood cells. The research shed light on the function of Pax5, which was one of about 100 genes known to 'suppress' human tumours. When these tumour suppressor genes were inactivated by changes to the DNA, cancers start to develop. Forcing B-ALL cells to resume their normal development could provide a new strategy for treating leukemia. By understanding how specific genetic changes drive B-ALL, it may be possible to develop more specific treatments that act faster with fewer side-effects. However genes that are lost in tumour cells are not traditionally drug targets as it is very difficult to develop drugs that restore the function of genes lost during cancer development. However by understanding the mechanisms by which Pax5 loss causes leukemia can begin to look at ways of developing drugs that could have the same effect as restoring Pax5 function. The genetic switch technology used to study Pax5 could also be used to understand 'tumour suppressor' genes in other cancers as well. Source: http://www.sciencedaily.com/releases/2014/06/140617094035.htm Contents Discovery Today Chloroplast tubes play a key role in plants' immune defense Researchers at University of California, Davis and the University of Delaware, Newark have found that chloroplasts better known for taking care of photosynthesis in plant cells, play an unexpected role in responding to infections in defense mechanism. Inter-organellar communication is vital for successful innate immune responses that confer defense against pathogens. However, little is known about how chloroplasts, which are a major production site of pro-defense molecules, communicate and coordinate with other organelles during defense. When plant cells are infected with pathogens, networks of tiny tubes called stromules extend from the chloroplasts and make contact with the cell's nucleus, the team discovered. The tubes are likely to deliver signals from the chloroplast to the nucleus that induce programmed cell death of infected cells and prepare other cells to resist infection. The work has been published online in the journal Developmental Cell (2015). Chloroplasts send out dynamic tubular extensions called stromules during innate immunity or exogenous application of the pro-defense signals, hydrogen peroxide (H2O2) and salicylic acid. Interestingly, numerous stromules surround nuclei during defense response, and these connections correlate with an accumulation of chloroplast-localized NRIP1 defense protein and H2O2 in the nucleus. These results support a model in which stromules aid in the transport of pro-defense signals into Infection causes tubes called stromules (blue) to grow from chloroplasts (purple) to the nucleus of a plant cell (yellow) carrying signals that boost immune defenses. the nucleus and other subcellular compartments during immunity. This opens a new area of understanding how the chloroplast communicates with the nucleus, and likely with other organelles within the cell. Chloroplasts in neighboring uninfected cells also produce stromules, apparently signaling the nucleus to switch on genes that make cells more resistant to infection. Stromules were first described more than 50 years ago, and their role in a specific biological process has been solved now. Source: http://www.sciencedaily.com/releases/2015/06/150625145244.htm Cutting Edge Contents Researchers have engineered the world’s first artificial ribosome Researchers in the US have developed a synthetic molecular structure called the Ribo-T and it can be placed inside a living cell to produce specialized proteins and enzymes at almost the same efficiency as an actual ribosome. Ribosomes are dense, complex structures inside all living cells, that catalyze a constant stream of protein chains by linking amino acids together in the order specified by messenger RNA (mRNA) molecules. These cellular workhorses are basically in charge of decoding DNA, and now scientists have manufactured a molecular device that can not only produce protein chains in a test-tube almost as well as a real ribosome, but can also churn out enough protein in bacterial cells without any natural ribosomes to keep them alive. The team from the University of Illinois at Chicago and Northwestern University, says not only will the Ribo-T help to better understand how our own ribosomes function, but it could lead to more effective drugs and next-gen biomaterials, with these little protein factors churning out whatever the need. Natural ribosomes float around inside a cell in two halves (or subunits), and only link up when they need to link some protein chains together. To keep the lab-made ribosome from linking up with the naturally occurring ones - which would kill World’s first engineered artificial ribosome the cell - the scientists tethered the two halves together. Because Ribo-T is tethered shut and can never separate like a natural ribosome, all kinds of new and amazing things can be cooked up inside, such as unique polymers that can help us track processes inside the ribosome. By creating an engineered ribosome where the ribosomal RNA is shared between the two subunits and linked by these small tethers, the scientists could actually create a dual translation system. While the engineered ribosomes exceeded all expectations in terms of how effective they are, they are far from perfect. Reporting in Nature, the team says that while bacterial cells with no natural ribosomes at all could live off the proteins produced by an army of Ribo-Ts, they grew at half the speed of normal cells. One of the scientists told that the tethered ribosome is good, but not as good as 'normal' ribosome". The team is hopeful that with a few years under its belt, Ribo-T be a whole lot more efficient than it is now. It’ll never catch up to the several billion years of evolution that our ribosomes have had to perfect their craft. Source: http://www.sciencealert.com/researchers-have-engineered-the-world-s-firstartificial-ribosome Our Focus Contents The Centre is involved in a wide range of research work like plant-pathogen interaction studies, study of active compounds in medicinal plants, in-silico analysis of phytochemicals against various diseases and creation of databases and their maintenance. In silico docking studies on phyto compounds are carried out to predict the preferred orientation of one molecule to a second when bound to each other to form a stable complex. The binding efficiency, interaction and dock score would help a long way in identifying novel phytocompounds against serious diseases. Contents Letters & Ideas This particular column is especially for readers and those who are interested in the field of Bioinformatics. Here we are creating a new opportunity to share your valuable ideas with senior scientists. So post your comments and suggestions to mail [email protected] or [email protected]. The Team Dr. P.A.Nazeem (Coordinator) Priyanka James, Radhika R., Ravisankar V., Bincy Baby, Vipin A.M., Sangeetha P. Davis & Cicy Joseph. How to Reach Us Bioinformatics Centre (DIC), ITBT Complex, Kerala Agricultural University, KAU P.O, Thrissur, Kerala-680656. Website: www.kaubic.in Email: [email protected], [email protected] or [email protected] Ph: 0487-2371994, Fax: 91487-2371994.