Genomic Medicines in the Developing World : Nature Reviews Genetics             Dhaka the 28th Sept., ’08. In a letter published in a special supplement of the October issue of Nature Reviews Genetics Abdallah Darr and associates brought to the attention of the readers to a series of four articles on the emergence of genomic medicine in emerging economies in the developing world. The articles highlight the human genomic variation studies of Mexico, India, Thailand and South Africa aimed at stimulating economic growth and local health benefits. GNOBB sincerely hope that these articles in turn will prompt the policymakers in Bangladesh to initiate similar activity in the country. Read the letter. Information conveyed by GNOBB member Prof. Naiyyum Choudhury                                                                                                        _______________________________________________ 

Signaling pathways & RNA processing: New findings shed light on mRNA maturation                                                                                                                    Dhaka 28th Sept., ’08. miRNAs are short 20-22 nucleotide RNA molecules that regulate gene expression in eukaryotic organisms. The first studied miRNAs were identified in C.elegans. Worms with mutations in these genes failed to pass through certain developmental stages. Cloning of these genes revealed that they are small non-coding trasncripts producingstem-loop structures. Aberrant expression of miRNAs leads to developmental abnormalities and diseases such as cardiovascular diseases and cancer. The processes that control the miRNA processing are largely unknown. Members of the TGFbeta family control vascular phenotype. Akiko Hata and associates in a recent article in Nature have demonstrated that the signaling molecules control vascular phenotype via modulating miRNA processing; and Smad transcription factors play an important role in this process. These findings open new avenues for the study of signaling pathways and RNA processing. Read the article. By GNOBB member Dr Talat Nasim

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Bird Flu Viral and Human Proteins Interaction may Provide Clue to Antiviral Drug Discovery

Launching of a New Subsection, “Molecular Biotechnology.”

Due to volume of scientific news, it was considered worthwhile to start subsections under different disciplines of biotechnology. Now the second subsection under the title, “Molecular Biotechnology”  is ready to be launched. The summary of a few of these write-ups mostly by Mr. Mahdi Moosa, an undergraduate in GEB, Dhaka University, have already appeared in GNOBB homepage.  According to the present arrangement, summaries of interesting articles on “Mol. Biotech.”  by GNOBB members or any student of this discipline will be on display for a month or so in GNOBB homepage and then transferred to this subsection. Pl. read Mahdi's introductory remarks   ____________________________________

finding, the picture of the crystal structure of this protein will feature in the 
cover page of the October issue of the journal. Read the abstract.
 

Ullah H, Scappini EL, Moon AF, Williams LV, Armstrong DL, Pedersen LC. Structure of a signal transduction regulator, RACK1, from Arabidopsis thaliana.

In collaboration with a NIH lab, Dr. Hemayet Ullah and his team have deduced the crystal structure of the Arabidopsis RACK1 protein. This is the very first report of a RACK1 structure. The structure will not only advance RACK1 mediated plant environmental stress signaling studies, but will also help  elucidate the structural basis of several neuropathologies in human as well. The Arabidopsis rack1a knock-out plants show drought resistance phenotype. Thus the structure will help investigate both physiological and structural basis of drought stress signaling pathways in plants.

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Gene (S5) Identified in Rice to Overcome Crossing Barrier bet.  2 Subspp. 
Dhaka, 23rd Aug. '08. In an article captioned, “A triallelic system of S5 is a major regulator of the reproductive barrier and compatibility of indica–japonica hybrids in rice appeared in the 22^nd Aug. edition  of PNAS vol. 321:1072- 1075, Qifa Zhang, the leader of the team  of 20 scientists report that in rice they have cloned a gene called S5 that separates the two subspecies, indica and japonica. The two alleles in the two subspecies have been named, S5-i and S-j for indica and japonica, respectively. S5 encodes for an aspartic protease contributing to embryo sac fertility.  The aspartic protease in the two subspecies differs only in respect of two nucleotides. In their germplasm collection,  these researchers  discovered a special group, designated wide-compatibility varieties (WCVs). Both indica and japonica when hybridized with wide-compatibility vars. yield fertile hybrids. This discovery of S5 will open up a wide range of opportunity to rice breeders in combining desirable genes from the two subspecies which were not hitherto possible due to hybrid sterility. We hope that active rice breeders will be in the forefront to take advantage  of utilizing triallelic gene S5 in enhancing further productivity and other qualities in BD varieties. Read the article. Readers may be interested to know about Ph1 (homeologus pairing ) gene in hexaploid bread wheat which has the opposite effect compared to S5 in that the Ph1 gene prevents pairing between homeolgous chromosomes between A, B and D genomes. More about Ph1 gene..

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Bioavailable Calcium in Bioengineered Carrot
Dhaka 24^th Aug, ’08. In a recent  paper, “Nutritional impact of elevated calcium transport activity in carrots,” published in PNAS  (105:1431-5),   researchers led by J. Morris affiliated to Texas A&M University and  Baylor College of Medicine in Texas have reported that  the transgenic  carrot  they have engineered provides 41% more absorbable calcium compared to the controls where the mineral is poorly absorbed. In the bio-engineered carrot strain, Ca²⁺   moves more freely across the cell membrane as a result of  incorporation of a transgene, sCAX1.  The claim by these scientists is based on an experiment on 30 individuals, 15 men and 15 women between the ages of 21 and 29 where they were given GM  carrot and their urine tested to determine the rate of Ca²⁺ absorption.   It is still a long way to go before sufficiently calcium-rich GM carrot would be available in the market eliminating the need of extra Ca²⁺ intake. Read more in a related article, Biofortified and bioavailable: The gold standard for plant-based diets.
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Methylene Blue may be a future cure  for Alzheimer’s and Parkinson’s Disease
Dhaka 21^st Aug., 2008. In the March issue of the Federation of American Societies for Experimental Biology Journal (The FASEB Journal. 2008;22:703-712), researchers led by Hani Atamna reported the results of their study  that extremely small doses of methylene blue - a drug discovered  in 1891; i.e., more than a century ago slows or even may cure Alz­heim­er’s and Park­in­son’s dis­ease. The group affiliated to Chil­dren’s Hos­pi­tal & Re­search Cen­ter Oak­land, in Cal­i­for­nia studied the effect of  methylene blue on lab­ora­tory-cultured cells and mice and found that in low dosages the chemical slows down the senescence of mitochondria and enhances key mitochondrial biochemical pathways by acting specifically on an im­por­tant en­zyme called com­plex IV.  The main reason why further study  with this chemical discontinued  was its known adverse effect causing brain damage.  It is only recently that the above group discovered that in an extremely low dosage it proves efficacious in the treatment of both Alz­heim­er’s and Park­in­son’s dis­ease.

It’s a suitable area where research in BD should be initiated. The low-cost treatment with methylene blue will be like aspirin used for blood thinning for heart patients.
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Allerginicity Risk of Transgene Proteins Not Significant to Those Allergic to Known Allergens 

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An Interesting Article on Transgenic Papaya in Plant Physiology
July 21st, '08. GNOBB readers specially those in doing work in GM crops and biosafety issues may be interested to read the following article which has been published in one of the recent issues of Plant Physiology. The full length article is available free online just a click away from the reader. Some important information about nutritive value of papaya fruit is that it supplies two of the three essential micronutrients, namely iron and vitamin A. A 100-g serving daily of ripe papaya supplies vitamin C and vitamin A in sufficient quantities to overcome micronutrient deficiencies. Here is a lesson to be learned by Bangladeshis which can be summed up by the statement of Dr. M. Abdul Momin, working in On-Farm Research Division, Bangladesh Agricultural Research Institute, Pabna, "Here people cannot afford vanity." 

Forbidden Fruit: Transgenic Papaya in Thailand by Sarah Nell Davidson.

 

Papaya Genomic Sequence Paper  by 85 Scientists  under the Leadership of Prof. Maqsudul Alam has been published today,  the 24th April Issue of Nature  Prof. Maqsudul Alam, ASGPB   Austin, 24th April, '08. The paper entitled, "The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus)" by  Prof. Maqsudul Alam and 84 Associates has featured in the 24th July edition of Nature,  including a cover page photograph of transgenic papaya plantation, Prof. Alam’s interview with the editor of Nature (452: 991-996) and the most recent press release by Advanced Studies in Genomics, Proteomics and Bioinformatics (ASGPB). GNOBB congratulate him and coworkers from the bottom of their hearts  on this outstanding feat. GNOBB members have no doubt in their mind that Prof. Alam will guide  biotechnologists in general and young scientists of Bangladesh in particular to put the country's name  in the forefront of Molecular Biology. Read the summary by clicking here. Congratulatory message from Dr. Firdausi Qadri,  Dr. Abed Choudhury, Prof. Ahmed Azad, and  Prof. Haseena,  Dr. Md. Tofazzal Islam __________________________ Increasing the efficiency of RNAi (RNA interference) mediated knockdown Dhaka 13th July, ’08. In a research article published in 8th July issue of PNAS (USA), Diederichs et al. report an novel method of increasing efficiency of RNAi mediated knockdown. One of the major problems with using RNAi is its variable efficiency and specificity. This complicates studies targeting individual genes and significantly impairs large-scale screens using genome-wide knockdown libraries. Diederichs et al. have shown that co-expression of Argonaute-2 protein along with interfering RNA gives uniform and highly specific target gene suppression. This observation has immediate applications for optimal design of RNAi strategies.Please click here for the article. Summarized by Mahdi Moosa, Genetic Engineering & Biotechnology, DU. ____________________________________________ Heartiest Congratulations to Dr. Mottaleb and Associates Dhaka 24th July, 2008. GNOBB heartily congratulate Dr. Mottaleb and his associates for their recent publication in the J. Environment Science.   M. A. Mottaleb (2008)  Biological transformation, kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure. J. Environ. Sci 20 (7), 878-884.  The research was designed to analyze the exposure of pharmaceutical and personal care products (PPCPs) in aquatic organisms such as fish.  The biotransformation, dose-response etc. assessments were made.  It has been proved that biotransformation of nitro musk (a fragrance ingredient) could be found in fish blood through hemoglobin adducts and could be used as biomarker of exposure.  In Bangladesh, pharmaceutical and other industrial companies are polluting water environment through discharging their wastes continuously;  as a result aquatic organisms are at risk in their own environment.  Since human consumes fish regularly through diet, consequently human and other fish-eating animals  are continuously facing health hazard. Because PPCPs form metabolites through enzymatic nitro-reduction or breakdown in living beings.| _________________________ Increasing the efficiency of RNAi (RNA interference) mediated knockdown Dhaka 13th July, ’08. In a research article published in 8th July issue of PNAS (USA), Diederichs et al. report an novel method of increasing efficiency of RNAi mediated knockdown. One of the major problems with using RNAi is its variable efficiency and specificity. This complicates studies targeting individual genes and significantly impairs large-scale screens using genome-wide knockdown libraries. Diederichs et al. have shown that co-expression of Argonaute-2 protein along with interfering RNA gives uniform and highly specific target gene suppression. This observation has immediate applications for optimal design of RNAi strategies.Please click here for the article. Summarized by Mahdi Moosa, Genetic Engineering & Biotechnology, DU.. _______________________ Regulation of translation through non-canonical upstream ORF (uORF) Dhaka 20th July, ’08. In an article published 22nd July, 2008 in PNAS USA, Ivanov et al. report the role of non-canonical upstream ORF (uORF) in translational regulation of mammals. There are several regulatory routes in Eukaryotic gene expression, many being discovered, while others remain to be unraveled. Recently various studies have revealed the role of upstream ORFs (uORF) which serve as an additional regulatory route. These uORFs show inhibitory effects in translation. Previously it was assumed that uORFs use AUG as their sole start codon but Ivanov et al. report that ornithine decarboxylase homologues in mammals have non-canonical evolutionarily conserved start codons as uORFs, the main one being AUU which serves as an autoregulatory circuit. Their study also illustrates the role of polyamine level as a new translation regulation device. Summarized by Mahdi Moosa, Genetic Engg & Biotech, DU.  ____________________________________________________ An Unexpected Finding  in Medical Science: Correlation breaks down between abundance of mosquitoes and Dengue Fever at a certain level. Dhaka, 23rd July, ’08. One of the main strategies of preventing vector-borne diseases is to reduce the number of vector itself.  However, this generalization does not hold good always such as in dengue haemorrhagic fever (DHF). In an article published online in the 16th July issue of PLOS Neglected Tropical Diseases, Thammapalo et al.  have shown that in DHF infection up to a certain level, there is a correlation between the number of  Ades mosquitoes and the incidence of Dengue fever-infected people. Beyond that threshold value, the correlation breaks down; i.e., the increased number of Ades mosquitoes over a threshold actually reduces the incidence of DHF as observed in the Dengue endemic region of Thailand. The authors explain the phenomenon: an increased number of Ades mosquitoes, creates a greater chance of secondary Dengue infection which provides cross-seroprotection through seroconversion. Click here to read more. Summarized by Mahdi Moosa, Genetic Engg & Biotech, DU.                                     __________________________________________________ Comments by GNOBB member Dr. Sultanul Aziz  The logic given in this note is well known in Medical science. However, beyond Dengue fever or similarly immunologically primed individuals, there are organisms that confer short term immunity; in other words the immunity acquired against a natural infection fades away in a few months which brings in additional variables in the equation. Perhaps a field of mathematical modelling awaits bioinformatics input for each variety of each serotype in order that we can predict the effect of each antigen on human (not to exclude the veterinary world) individuals who themselves have varied capacity to produce antibodies against specific antigens. ___________________ Nuclear RNA interference: A long Sought Proof unraveled  Dhaka 27th July, '08. In a research article published online 25th July of Science, Guang et al. report nuclear localization of RNAi and its mechanism. Small regulatory RNAs (siRNAs, miRNAs) regulate gene expression through RNAi. It was thought that this process can be carried out in both the cytoplasm and the nucleus, but hitherto there was no evidence for nucleus being the location.  Guang et al. report the role of NRDE-3 (Nuclear RNAi Defective), an argounate protein. In the absence of regulatory RNAs, this protein resides in the cytoplasm of Caenorhabditis elegans. But upon binding to regulatory RNAs like siRNAs, NRDE-3 moves to the nucleus where it breaks down the RNA molecules which have significant sequence complementarity.__________________________ An Open Source platform for building customized Zinc Finger Nucleases  Dhaka 30th July, ’08. Targeted DNA modification is the very first step of an efficient gene therapy. Present techniques rely on non-specific delivery by different viruses or delivery through homologous recombination (HR). Both of these processes are not much efficient. An alternative to this approach is introduction of Double Stranded Break (DSB) to targeted location of DNA. Repair of DSB by cellular mechanisms greatly increases both rate and efficiency of HR-mediated gene targeting with an exogenous DNA molecule. DSB can be introduced by engineered Zinc Finger Nucleases (ZFN). In a paper describing this technique published 25th July 2008 in Molecular Cell,  Maeder et al. describe an efficient and rapid method for ‘‘Open-Source’’ engineering of customized Zinc-Finger Nucleases for highly efficient gene modification through OPEN (Oligomerized Pool ENgineering) platform. Because OPEN is rapid, reliable, and publicly available, it will foster wider usage and  large scale applications of engineered zinc-finger technology. Summarized by Mahdi Moosa, Genetic Engg and Biotech, DU. _____________________________ GM Crop Put to a Different Use for Clearing Land Mines Dhaka the 29th July, 2008. South African scientists from the University of Stellenbosch have bio-engineered a tobacco strain that turns red when it grows near a land mine. Many of the war-ravaged countries such as Angola, Afghanistan, Burundi, Bosnia- Herzegovina, Cambodia, Chechnya, Colombia, Iraq, Nepal and Sri Lanka are filled with land mines endangering the lives of those who live nearby. At present endangering their lives only explosive experts can clear these areas at an exorbitant cost aided by sniffer dogs. Using the model plant, Arabidopsis thaliana, a tiny weed, scientists developed a technology called ‘RedDetect’. Upon exposure of its roots to the byproducts of land mines such as nitrogen dioxide leaching from the soil, the tiny herb turns autumnal red from its natural green color. Since the weed is too small to be detected from a distance, scientists have developed this GM tobacco strain, large enough to overcome the sighting problem. The SA Univ. and a Danish Biotech firm will be jointly undertaking biosafety trials in the affected countries before it is marketed to make the war wrecked regions much safer to live at a fraction of the present cost. Read More in the original article. _____________________________________ Seminar on Biotechnology on 30th July at BRAC University  Dhaka 27th July, ’08. Prof. Naiyyum Choudhury, Coordinator, Biotechnology Program at BRAC University informs GNOBB   that the Department of Mathematics and Natural Sciences at his University has arranged a seminar captioned, “The New Biology: the Network Metaphor,” to be held on Wednesday the 30 July 2008 at 4:00 PM in UB 104. The speaker, Dr. Animesh Ray,  Professor in Systems Biology, Keck Graduate Institute, at Claremont, USA is a celebrity in Modern Biotechnology. Prof. Ray and his associates discovered a new genetic pathway for specifying ovule development in flowering plants. Subsequently, they cloned and patented a gene named DICER-LIKE1 (DCL1) that controls the production of micro RNA in flowering plants.Their unique contribution has elucidated our understanding as to how  a large number of genes control essential plant development and its various functions such as flowering and embryogenesis, including the role of RNA silencing to plant development. _____________________________________ Seminar on Systems Biology in BRAC University Concluded Dhaka, 30th July, 2008. The audience comprising the Vice Chancellor Jamilur Reza Choudhury, Dr. Abed Chaudhury, Prof. Naiyyum Choudhury, Professor Haseena Khan, Prof. Ahmad Islam among others was captivated by the lecture delivered by Prof. Animesh Ray on, “The New Biology: the Network Metaphor.”  He started his talk on drawing a line of distinction between Engineering and pure science. He traced the history that led to the establishment of the new discipline  called “Systems Biology,” where three disciplines, namely, Engineering, Computer Science and Biology have integrated allowing us to understand the complex phenomena of biology such as the multitude of genes that trigger vegetative phase of yeast to that of sporulation. Aided by complex algorithm, latest technique of molecular biology and  sophisticated engineering design their team has now turned their attention from mice to the genes that are directly involved in causing diseases related to hypertension, diabetes. Although a long way to go they appear on the right track and they hope to find solution for the efficacious treatment of such metabolic disorders in the not too distant a future.   _________________________  Hybrid rice cultivation  in Bangladesh  is on the increase by app. 100 per cent Austin 23rd March, ’08.  Thanks to the effort of the Government that rice farmers have grown hybrid rice in the ‘boro’ season  in over seven lakh hectares compared to 3.9 lakh ha last year. Farmers were motivated to grow more rice to ensure food security and to face the challenge of food shortage in the wake of devastating twin flood and the cyclone ‘Sidr’.  Hybrid rice is one good example as to how biotech helps us in enhancing production of  staple food crops such as rice during the time of emergency when food is needed most. The yield of hybrid rice such as Hira, Aloron, Jagoron, Sonar Bangla and Moina, is 20-30% higher than HYV’s, input of fertilizers and other practices remaining the same, initially under the supervision and management of rice hybrid experts.  Read More… __________________________ The Maternal control of MET1 on Seed Size of Arabidopsis Dhaka June 1st , 2008. Jonathan FitzGerald, Abed Chaudhury and their associates have published an article entitled, “DNA Methylation Causes Predominant Maternal Controls of Plant Embryo Growth” online in Public Library of Science  (PLoS ONE) 3(5), an open access journal. By a series of elegant experiments, they have demonstrated the influence of MET1 (methyl transferase1) gene on the male and female gametophytic development and their effect on seed size. For instance,  loss of MET1 during male gametogenesis results in a reduction of seed size. On the other hand, seed size is increased considerably consequent on the reduction of MET1 dosage in the maternal somatic tissue, the dominant allele MET1 being responsible for limiting cell division  and elongation of integuments surrounding the ovule.  To the contrary, when the recessive allele met1 is contributed by the female  parent, seed size is increased. Their results lead them to conclude that the embryo growth is regulated by MET1 in which the control is largely by the female parent. __________________________ Antidote for Deadly Botulinum Neurotoxin in sight: work of two famous USA labs.  Austin, April 29th. '08. Scientists at the U.S. Department of Energy's Brookhaven National Laboratory and the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) have taken the first step toward designing an effective antidote to the most potent of seven neuro- toxins produced by the bacterium Clostridium botulinum. The results of this outstanding work have been published in the April 22, 2008 online issue of J. Biol. Chemistry in an article captioned, “Structure and substrate based inhibitor design for  Clostridium botulinum neurotoxin serotype A”. Dr. S. Ashraf Ahmed USAMRIID, the principal investigator and one of the authors of the above publication initiated the structure-based inhibitor design as part of the Institute's bio-defense research program. Dr Ashraf remarked, "We are excited about the success of this work and the prospects it holds for future drug development."  Read more .... GNOBB congratulate heartily to its member Dr. S. Ashraf Ahmed and his associates for their achievement - communicated by Dr. S. Ashraf Ahmed. Read congratulatory messages from Professor Azad, Dr. Parvez Haris. The two messages also contain a number of suggestions on the ways and means to promote biotech BD. _______________________________ Activation of Multiple resistance to Psedudomonas by treatment with Penicillium simplicissimum Austin December 23, 2007. In the following article published by GNOBB member, Md. Motaher Hossain,  as a lead author and his associates showed that the Arabidopsis thaliana  plants,grown in soil amended with barley grain inocula of GP17-2 strain of Penicillium simplicissimum were resistant to  Pseudomonas syringae pv. tomato DC3000 (Pst), the bacterium that causes bacterial speck of tomato. They obtained similar results when the roots of the plant were treated with the culture filtrate (CF) of  the Penicillium sp. In order to critically study the role of GP17-2, they compared its action with those of  Arabidopsis genotypes involved in salicylic acid (SA) signaling expressing the NahG transgene or carrying disruption in NPR1 (npr1), jasmonic acid (JA) signaling (jar1) and ethylene (ET) signaling (ein2). The comparative study of local and systemic gene expression revealed that GP17-2 and its CF elevate the expression of genes involved in both the SA and JA/ET signaling pathways conferring multiple resistance to the bacterial speck of tomato caused by Pst. The abstract from the original article is only a click away when you hit the highlighted title below: GNOBB congratulate the lead author, the team leader, Prof. M. Hyakumachi and associates.

YABBY-like Transcription Factor Responsible for  Extra Large Tomato Fruit Size

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