International Centre For Genetic Engineering And Biotechnology Research Articles

A Curriculum-Based Approach to Teaching Biosafety Through eLearning.

Anyone working in biosafety capacity enhancement faces the challenge of ensuring that the impact of a capacity enhancing activity continues and becomes sustainable beyond the depletion of funding. Many training efforts face the limitation of one-off events: they only reach those people present at the time. It becomes incumbent upon the trainees to pass on the training to colleagues as best they can, whilst the demand for the training never appears to diminish. However, beyond the initial effort to establish the basic content, repeating capacity enhancement events in different locations is usually not economically feasible. Also, the lack of infrastructure and other resources needed to support a robust training programme hinder operationalizing a “train-the-trainer” approach to biosafety training. One way to address these challenges is through the use of eLearning modules that can be delivered online, globally, continuously, at low cost, and on an as-needed basis to multiple audiences. Once the modules are developed and peer-reviewed, they can be maintained on a remote server and made available to various audiences through a password-protected portal that delivers the programme content, administers preliminary and final exams, and provides the administrative infrastructure to register users and track their progress through the modules. Crucial to the implementation of such an eLearning programme is an approach in which the modules are intentionally developed together as a cohesive curriculum. Once developed, such a curriculum can be released as a stand-alone programme for the training of governmental risk assessors and regulators or used as accredited components in post-graduate degree programmes in biosafety, at minimal cost to the government or university. Examples from the portfolio of eLearning modules developed by the International Centre for Genetic Engineering and Biotechnology (ICGEB) are provided to demonstrate these key features.

Promoterless gene targeting without nucleases rescues lethality of a Crigler-Najjar syndrome mouse model.

Crigler‐Najjar syndrome type I (CNSI) is a rare monogenic disease characterized by severe neonatal unconjugated hyperbilirubinemia with a lifelong risk of neurological damage and death. Liver transplantation is the only curative option, which has several limitations and risks. We applied an in vivo gene targeting approach based on the insertion, without the use of nucleases, of a promoterless therapeutic cDNA into the albumin locus of a mouse model reproducing all major features of CNSI. Neonatal transduction with the donor vector resulted in the complete rescue from neonatal lethality, with a therapeutic reduction in plasma bilirubin lasting for at least 12 months, the latest time point analyzed. Mutant mice, which expressed about 5–6% of WT Ugt1a1 levels, showed normal liver histology and motor‐coordination abilities, suggesting no functional liver or brain abnormalities. These results proved that the promoterless gene therapy is applicable for CNSI, providing therapeutic levels of an intracellular ER membrane‐bound enzyme responsible for a lethal liver metabolic disease.

Targeting of surface alpha-enolase inhibits the invasiveness of pancreatic cancer cells.

Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive malignancy characterized by rapid progression, invasiveness and resistance to treatment. We have previously demonstrated that most PDAC patients have circulating antibodies against the glycolytic enzyme alpha-enolase (ENO1), which correlates with a better response to therapy and survival. ENO1 is a metabolic enzyme, also expressed on the cell surface where it acts as a plasminogen receptor. ENO1 play a crucial role in cell invasion and metastasis by promoting plasminogen activation into plasmin, a serine-protease involved in extracellular matrix degradation. The aim of this study was to investigate the role of ENO1 in PDAC cell invasion. We observed that ENO1 was expressed on the cell surface of most PDAC cell lines. Mouse anti-human ENO1 monoclonal antibodies inhibited plasminogen-dependent invasion of human PDAC cells, and their metastatic spreading in immunosuppressed mice was inhibited. Notably, a single administration of Adeno-Associated Virus (AAV)-expressing cDNA coding for 72/1 anti-ENO1 mAb reduced the number of lung metastases in immunosuppressed mice injected with PDAC cells. Overall, these data indicate that ENO1 is involved in PDAC cell invasion, and that administration of an anti-ENO1 mAb can be exploited as a novel therapeutic option to increase the survival of metastatic PDAC patients.

Translational selection in human: more pronounced in housekeeping genes.

BackgroundTranslational selection is a ubiquitous and significant mechanism to regulate protein expression in prokaryotes and unicellular eukaryotes. Recent evidence has shown that translational selection is weakly operative in highly expressed genes in human and other vertebrates. However, it remains unclear whether translational selection acts differentially on human genes depending on their expression patterns.ResultsHere we report that human housekeeping (HK) genes that are strictly defined as genes that are expressed ubiquitously and consistently in most or all tissues, are under stronger translational selection.ConclusionsThese observations clearly show that translational selection is also closely associated with expression pattern. Our results suggest that human HK genes are more efficiently and/or accurately translated into proteins, which will inevitably open up a new understanding of HK genes and the regulation of gene expression.ReviewersThis article was reviewed by Yuan Yuan, Baylor College of Medicine; Han Liang, University of Texas MD Anderson Cancer Center (nominated by Dr Laura Landweber) Eugene Koonin, NCBI, NLM, NIH, United States of America Sandor Pongor, International Centre for Genetic Engineering and biotechnology (ICGEB), Italy.

Prolyl‐isomerase Pin1 controls normal and cancer stem cells of the breast

Mammary epithelial stem cells are fundamental to maintain tissue integrity. Cancer stem cells (CSCs) are implicated in both treatment resistance and disease relapse, and the molecular bases of their malignant properties are still poorly understood. Here we show that both normal stem cells and CSCs of the breast are controlled by the prolyl-isomerase Pin1. Mechanistically, following interaction with Pin1, Notch1 and Notch4, key regulators of cell fate, escape from proteasomal degradation by their major ubiquitin-ligase Fbxw7α. Functionally, we show that Fbxw7α acts as an essential negative regulator of breast CSCs' expansion by restraining Notch activity, but the establishment of a Notch/Pin1 active circuitry opposes this effect, thus promoting breast CSCs self-renewal, tumor growth and metastasis in vivo. In human breast cancers, despite Fbxw7α expression, high levels of Pin1 sustain Notch signaling, which correlates with poor prognosis. Suppression of Pin1 holds promise in reverting aggressive phenotypes, through CSC exhaustion as well as recovered drug sensitivity carrying relevant implications for therapy of breast cancers.

Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa

Molecular mechanisms of viral infection and propagation: An overview of the second Advanced Summer School in Africa

The molecular and cellular basis of infection—Perspectives from the first advanced summer school in Africa

The molecular and cellular basis of infection—Perspectives from the first advanced summer school in Africa

El Sur también existe: processing RNA in the Argentine Patagonia

The meetings on ‘Cell Biology, Signaling and Alternative Splicing’ and ‘Gene Expression and RNA Processing’ took place between 26 and 30 November 2007, in Bariloche, Argentina, and were organized by A. Kornblihtt, A. Srebrow, J. Caceres, A. Lamond and T. Misteli. Support was provided by the International Centre for Genetic Engineering and Biotechnology (ICGEB) and by the European Network on Alternative Splicing (EURASNET). ![][1] “El Sur tambien existe” However down here,down close to the roots,is where memoryforgets no memories.And there are those who struggleand there are those who try hardand this is how together they managewhat seemed impossible.The whole world knowsthat the South,the South also exists. Mario Benedetti (translated by J. Martinez) The heart of science also beats in the southern hemisphere, and in the last days of November 2007, in the middle of the southern spring, the RNA community met in Bariloche, in the beautiful Argentine Patagonia. Transcription and RNA processing were the focus of the combined meetings ‘Gene Expression and RNA Processing’ and ‘Cell Biology, Signaling and Alternative Splicing’. The organizers chose a lovely site, as well as an eclectic group of speakers and participants. The result was a stimulating mixture of science, lively poster sessions with students and postdocs, and hours of informal discussion. Here, from the 52 talks presented, we strive to highlight selected emergent themes and apologize to those speakers whose topics we have been unable to include. The meeting started with a Keynote Lecture from T. Cech (Boulder, CO, USA), whose talk on telomerase foreshadowed many of the subsequent topics. Telomerase, the enzyme that extends chromosome ends and thereby maintains chromosome integrity over infinite cycles of DNA replication and cell division, uses an RNA primer provided by the telomerase RNA—Tlc1 in budding yeast and Ter1 in fission yeast (Zappulla & Cech, 2006). Similar to spliceosomal … [1]: /embed/graphic-1.gif

New Vaccine Strategy

NEW DELHI— In a new approach to vaccine development, a U.S. university will dispatch faculty members to India to help run a new vaccine research center with Indian partners. Until now, U.S. researchers have spent only a few months at a time in India, says Altaf A. Lal, a malaria researcher with the U.S. Embassy in New Delhi. Emory University's School of Medicine in Atlanta, Georgia, will spend $3 million over 3 years to hire three faculty members for the Emory Vaccine Center, a joint venture with the International Centre for Genetic Engineering and Biotechnology (ICGEB) in New Delhi. Tops on the center's list is developing a DNA vaccine against clade C of the HIV virus, developed by a team led by Emory University's Rama Rao Amara, a researcher running U.S. phase I clinical trials on a related virus. ICGEB Director Virander Singh Chauhan says the new center does not intend to use Indians as unwitting guinea pigs for new vaccines—an allegation that has dogged some of the more recent Indo-U.S. vaccine trials in India.

Nuclear factor TDP-43 and SR proteins promote in vitro and in vivo CFTR exon 9 skipping.

Alternative splicing of human cystic fibrosis transmembrane conductance regulator (CFTR) exon 9 is regulated by a combination of cis-acting elements distributed through the exon and both flanking introns (IVS8 and IVS9). Several studies have identified in the IVS8 intron 3' splice site a regulatory element that is composed of a polymorphic (TG)m(T)n repeated sequence. At present, no cellular factors have been identified that recognize this element. We have identified TDP-43, a nuclear protein not previously described to bind RNA, as the factor binding specifically to the (TG)m sequence. Transient TDP-43 overexpression in Hep3B cells results in an increase in exon 9 skipping. This effect is more pronounced with concomitant overexpression of SR proteins. Antisense inhibition of endogenous TDP-43 expression results in increased inclusion of exon 9, providing a new therapeutic target to correct aberrant splicing of exon 9 in CF patients. The clinical and biological relevance of this finding in vivo is demonstrated by our characterization of a CF patient carrying a TG10T9(DeltaF508)/TG13T3(wt) genotype leading to a disease-causing high proportion of exon 9 skipping.

Biotechnology and sustainable development in sub-Saharan Africa

Whether development is defined by the long-standing economic parameter of per capita gross national product (GNP) or by the newly introduced Human Development Index (HDI), which is not based exclusively on per capita GNP, the countries of sub-Saharan Africa rank at or near the bottom of the developing world. Agriculture and agro-based processing are the mainstays of the economies of the majority of these countries. Because of this, and also because many of the diseases endemic in these countries are communicable, the application of modern biotechnology (including genetic engineering, tissue culture and monoclonal antibody technology) and related biotechnologies could play an important part in creating sustainable development in the region. There is, therefore, an urgent need to train more of the region's indigenous citizens, and to equip more laboratories, in modern biotechnology. It is suggested that, in order to accelerate the harnessing of the fruits of biotechnology, more countries in the region should affiliate with the International Centre for Genetic Engineering and Biotechnology (ICGEB). It is further suggested that a regional equivalent of the ICGEB be built and the services of non-governmental biotechnology organizations used.

Agenda 21: biotechnology at the United Nations Conference on Environment and Development.

Preparation has yet to be completed for the 1992 Earth Summit UN Conference on Environment and Development (UNCED) in Rio de Janeiro Brazil. Nonetheless it has been planned as a forum in which recommendations will be made to governments and international organizations on how to alleviate environmental damage caused by human activities and how to prevent future damage without retarding development in the Third World. It will declare basic principles for national and individual conduct regarding environmental preservation and sustainable development; adopt international conventions to protect biodiversity and manage climatic change; lay out Agenda 21 activities as specified by UNCED; provide an agenda to help Third World governments manage environmental matters; and provide an agenda for improving the transfer of technology to developing countries. Where biotechnology is concerned scientists and policy makers in developing countries have shown their interest. Limited resources and capabilities however constrain their abilities to engage in serious research and development. International organizations such as the UN Industrial Development Organization (UNIDO) may help UNCED and developing countries with biotechnology. Since 1986 UNIDO has held the International Centre for Genetic Engineering and Biotechnology (ICGEB) as a special project. The ICGEB conducts research and development (RD trains scientific and technical personnel from member countries in advanced biotechnology techniques; helps member countries implement and operate ICGEB-affiliated RD and manages an information exchange for internationally affiliated centers. To maximize the potential of biotechnology to help Third World nations clear their environments of pollutants while safely exploiting natural resources organizations should promote full use of available training resources; promote biosafety and the dissemination of information on risk assessment and risk management; increase funding to support existing information networks; help make equipment and supplies available to developing countries; help bridge the gap between research and applications by encouraging universities and research institutions to market their research; and promote entrepreneurship in developing countries.

The international centre for genetic engineering and biotechnology: A new international scientific organization

How will the developing countries best employ the advanced biotechnologies, particularly genetic engineering, to help solve their problems and further development? One mechanism to help the Third World gain the requisite capabilities is being set up by the United Nations Industrial Development Organization (UNIDO), namely the International Centre for Genetic Engineering and Biotechnology (ICGEB). Made up of two components in New Delhi, India, and Trieste, Italy, it has four major functions: to perform research of importance to the Third World; to train scientific personnel from developing countries; to be a conduit for the international transfer of scientific and technical information; and to be the focal point of a network of affiliated national and regional R&D centers. The long and tortuous process of establishing the ICGEB is described. The reasons for the actions taken are analyzed, as are the real and potential problems facing the Centre.