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Report of a Meeting held on September 27-29, 2012 In Tashkent, Uzbekistan
Future Opportunities for U.S. - Uzbekistan Cooperation in the Life Sciences
Prepared by the American Association for the Advancement of Science andthe Academy of Sciences of the Republic of Uzbekistan
FUTURE OPPORTUNITIES FOR U.S. ‐ UZBEKISTAN COOPERATION IN THE LIFE SCIENCES
Workshop Summary Tashkent, Uzbekistan
September 27‐29, 2012
Organized and Prepared by: Gwenaële Coat, American Association for the Advancement of Science
Ibrokhim Abdurakhmonov, Academy of Sciences of the Republic of Uzbekistan Norman Neureiter American Association for the Advancement of Science
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Acknowledgements We would like to thank the panelists and meeting attendees who provided valuable and robust discussion and helpful comments on the report. We would like to acknowledge and thank the U.S. Department of State for their generous support of this meeting. We would like to thank the Academy of Sciences of Uzbekistan for their contributions and support for this meeting. We would like to thank Kavita M. Berger for contributing to the report and Andrew Amis for contributing to this meeting. Disclaimer The concerns or suggestions outlined in this report reflect the discussions at the workshop and do not necessarily represent the views of the AAAS Board of Directors, its Council, or membership or the Academy of Science of Uzbekistan leadership and membership. Printed in the United States © Copyright 2013 American Association for the Advancement of Science 1200 New York Avenue, NW Washington, DC 2005
About AAAS The American Association for the Advancement of Science (AAAS) is the world’s largest general scientific society and publisher of the journal, Science (www.sciencemag.org). AAAS was founded in 1848, and serves 262 affiliated societies and academies of science, reaching 10 million individuals. Science has the largest paid circulation of any peer‐reviewed general science journal in the world, with an estimated total readership of 1 million. The non‐profit AAAS (www.aaas.org) is open to all and fulfills its mission to “advance science and serve society” through initiatives in science policy, international programs, science education, and more. Academy of Sciences of the Republic of Uzbekistan The Academy of Sciences of the Republic Uzbekistan (AS RUz), http://www.academy.uz/en/about/index.php), established in 1943, is the largest scientific organization in the country for carrying out fundamental and applied research; transitioning the results of such research into technologies; and coordination of scientific studies. The Academy of Sciences includes 28 scientific research institutions and organizations, and accounts for more than 5,200 scientific staff members, including over 2,070 scientific workers, 85 Academicians, 370 Doctors, and 900 Candidates of Science. The Academy of Sciences publishes a dozen scientific journals, a couple of them are translated into English, and a popular science magazine. The Academy represents three main groups of disciplines: physical and mathematical sciences and engineering; chemical, biological and earth sciences; and social sciences and the humanities.
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History of U.S.‐Uzbekistan Cooperation
Since the Republic of Uzbekistan’s independence in the early 1990s, Uzbekistan has implemented several national and international programs to develop its science and technology research and education infrastructure to support a modern knowledge‐based economy. This investment focuses on science and technology policy activities with potential impact on socio‐economic development of the country. In the life sciences, the most prevalent issues of interest for Uzbekistan are agriculture, water and land resource management, health care, and biotechnology. Following its independence, the United States Government has been interested in long‐term scientific engagement with Uzbekistan, as well as other former Soviet Union countries. Starting in 2002, more than twenty mutually‐beneficial bilateral cooperative projects have been funded through the U.S. Department of Agriculture (USDA) Agricultural Research Service (ARS), with support from the Department of State or Department of Defense.1 For over a decade, USDA and Uzbek scientists have worked together to build long‐term research partnerships, develop genetically enhanced cotton varieties, and promote technology transfer, patenting of newly developed products, and responsible science. The USDA‐ARS programs were the most successful of all U.S. Government supported programs because their activities were based on mutually beneficial research interests such as cotton research and built on Uzbekistan’s agriculturally‐based economy. Furthermore, in December 2010, both countries signed a Science and Technology (S&T) Cooperation Agreement to “strengthen scientific capabilities, broaden and expand the extensive S&T communities of both countries, and promote S&T cooperation in areas of mutual benefit for peaceful purposes,” according to the countries’ respective S&T strengths and resources.2 The Agreement specifies that cooperation involve:
“Exchange of information, skills and technologies;
Exchange of scientists, experts, and other technical specialists;
Convening of seminars, conferences and meetings;
Training, retraining and enhancing skills of scientists, experts, and other technical experts;
Conducting joint research projects and studies;
Establishing scientific partnerships for implementing projects with the involvement of the private sector; and
Other mutually agreed forms of scientific and technological cooperation.” Finally in 2011, Dr. Alice Gast, President of Lehigh University, travelled to Uzbekistan under the U.S. Science Envoy program to “further relations between the U.S. and Uzbekistan in science
1 More information is retrievable at: http://www.ars.usda.gov/Research/docs.htm?docid=1026 2 More information is retrievable at: http://www.state.gov/r/pa/prs/ps/2010/12/152267.htm
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and education and identify opportunities for cooperation in energy, education, public‐private partnerships, and information technology”.3 Follow‐on support for collaborative scientific programs involving several different sectors from both countries is of great interest to both Dr. Gast4 That same year, the U.S. Department of State asked the American Association for the Advancement of Science (AAAS) to help identify opportunities for cooperation between U.S. and Uzbek life scientists. The AAAS Center for Science Diplomacy and Center for Science, Technology, and Security Policy initiated a collaborative partnership with the Academy of Sciences of the Republic of Uzbekistan (AS RUz) to convene two workshops – one in Uzbekistan and the other in the United States ‐ to help identify future bioengagement opportunities between the two countries. This report describes the first of these meetings by first describing the workshop itself, listing near and long‐term collaboration opportunities, and discussing the essentials for successful cooperation. The appendices of the report include the list of participants, workshop agenda, and a detailed listing of the research efforts presented at the workshop.
The Tashkent Workshop The Tashkent workshop, which was jointly hosted by AAAS and AS RUz on Sept 27‐29, 2012, focused on broad disciplinary areas within the environmental, agricultural, and human health sciences, which were also mentioned in the 2010 U.S.‐Uzbekistan S&T Agreement. Workshop participants consisted of prominent scientists from AS RUz institutes, Research Institutes of Uzbekistan’s Ministry of Agriculture and Water Resources and Ministry of Health, several U.S. universities, and the USDA‐ARS. The workshop consisted of a combination of scientific presentations from Uzbek scientists and their U.S. counterparts, and interactive discussion among all participants to identify potential collaborative areas of mutual interest and benefit. In the environmental and agricultural sciences sessions, presenters discussed the successful decade‐long collaborative program in which scientists worked at furthering developments in agricultural production and irrigation. The workshop also focused on the future, including such topics as the effects of climate change on crops. In the human health science sessions, presenters discussed existing capacity and techniques in both countries to identify treatments for infectious diseases and cancers. Past achievements and on‐going programs that were highlighted during the workshop prompted participants’ eagerness to pursue collaborative opportunities identified during the discussions. However, the major challenge facing both U.S. and Uzbek scientists is the availability of financial resources dedicated to the cooperative activities discussed at the workshop,
3 More information is retrievable at: http://www.state.gov/r/pa/prs/ps/2011/06/166536.htm 4 Norman P. Neureiter, AAAS‐CSTSP Acting Director, Personal communication, January 2012
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included in the S&T Cooperation Agreement, and identified during Dr. Gast’s visit. Despite the lack of available funding, interest by the two countries to promote scientific cooperation has not diminished. Indeed, meeting participants were optimistic that the United States and Uzbekistan would recognize the value of cooperation and find financial support for such activities, particularly since both countries could mutually benefit from addressing scientific challenges in a collaborative environment.
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Opportunities for Future Cooperation in the Life Sciences between the United States and Uzbekistan
During the scientific presentations and follow‐on discussions, workshop participants identified near and long‐term opportunities for research collaboration. Participants supported sustaining existing cooperative efforts in cotton research to ensure that the robust scientific partnerships forged over the last decade persist well into the future. Participants also advocated for expanding cooperation to new research activities in agriculture, environmental sciences (including water management and climate change), and human health. The high quality of presentations from both the U.S. and Uzbek life scientists provided a supportive environment for identifying areas of opportunities to further science and technology research ties.
Opportunities for Near‐Term Collaboration The following list of opportunities represent the near term research cooperation activities that were identified during the discussion for both Agricultural and Environmental Session and Human Health Science Session. Meeting participants believed that many of these research activities may be attained or at least initiated with a minimum amount of effort and funding.
Building a knowledgeable and capable workforce to meet Uzbekistan’s desire to develop genomics and bioinformatics capabilities for research areas beyond cotton research and sustain such capabilities in cotton genomics. Topics targeted for future research include:
o climate change and its effects on agricultural, environmental and food and agriculture biosecurity related issues;
o research on the development of drought resistant crops and efficient irrigation systems to increase water conservation and crop yields;
o cancer research, which is of mutual interest to both countries; o study of the molecular mechanisms of action of natural compounds that could be
used to prevent or treat cancers, infectious diseases, or other non‐communicable diseases.
Fostering existing exchange programs (e.g., Fulbright Fellowship), opening existing programs to Uzbek scientists (e.g. Borlaug Fellowship), and establishing new exchange programs. Such efforts would provide U.S. and Uzbek scientists with opportunities for information sharing, knowledge transfer, and skill development in several research areas, including genomics and bioinformatics. Workshop scientists were enthusiastic about nurturing bilateral exchange programs. While such programs would benefit scientists at all levels of experience and career stage, workshop participants stressed the
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importance of including and mentoring early‐career scientists for promoting development of long‐term scientific relationships.
o Through exchange programs, scientists could improve experimental procedures, such as next generation DNA sequencing and gene expression profiling methods, and/or training scientists on the design of research projects, including selection of experimental models, data collection and analysis, experimental techniques (e.g., gene therapy and oncological methods); best practices and research standards for specific research areas, such as genomics5, proteomics6, transcriptomics7, and metabolomics8; and newly emerging technologies, such as irrigation control systems and plant stress sensing, and their appropriate uses. Such training programs would bring modern research models and platforms to Uzbek scientists and enhance their access to highly competitive international scientific research. Training could be provided informally within the laboratory at either U.S. or Uzbek institutions or formally through short training courses at the host institution.
o As an added benefit, exchange programs would expand the network of scientists from the United States and Uzbekistan having similar understanding of responsible research science and the scientific method. By exposing Uzbek life scientists to best practices, for improving scientific methods or enhancing safe and responsible conduct of science, they could, once returned to their home laboratory, share lessons learned with their peer. Moreover, if organized, this group of scientists may form a formal network of Uzbek scientists, who could serve as ambassadors for promoting responsible research practices with scientists from other former Soviet Union countries as well.
Mentoring of early‐career students. Including both Uzbek and U.S. scientists on the thesis committees of masters’ or doctoral students involved in bilateral research activities would increase access to foreign scientists with whom long‐term scientific and mentorship relationships could be developed.
Technological Transfer. Funding projects that are close to commercialization could result in long‐term benefit of cooperative projects and facilitate a return on investment.
5 Genomics is the study of genomes of organisms. Epigenomics represents modifications of the DNA and of the
chromosomal histone proteins that contribute to activation or silencing of expression of genes. 6 Proteomics is the study of an organism's complete complement of proteins, including function and structure 7 Transcriptomics is the study of the set of all RNA molecules, including mRNA, rRNA, tRNA, miRNA, and non-coding
RNA produced in cells. 8 Metabolomics is the study of chemical processes involving metabolites, such as sugars and fats.
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Opportunities for Long‐term Collaboration
Agricultural and Environmental Research During the discussion sessions related to agricultural and environmental research, participants also identified opportunities for long‐term collaboration. The following list catalogs such possible cooperative activities.
Continuing and enhancing current joint research activities on cotton genomics and bioinformatics focusing on characterization, cloning, and mapping agronomically important traits and genes for quality, resistance to pathogens and pests, and tolerance to harsh climatic conditions (e.g., salinity and drought). These studies would develop improved crop varieties, which could contribute to sustainable cotton production in the United States and Uzbekistan, using new genome editing techniques and transgenomic tools.
Expanding genomics‐based research efforts to other priority crops in both countries. Examples of such research efforts include developing varieties of wheat that are resistant to pests, pollutants, drought and other weather‐related problems, and water salinity, and improving the nutrient content of wheat and other commodities. Lessons learned from past successful cooperative research activities on cotton could serve as a basis for successful collaborative efforts on wheat and other agricultural products of importance to the United States and Uzbekistan.
Expanding and optimizing irrigation systems and related soil salinization research efforts, and improving agronomic practices. These research efforts may result in increasing crop yields per unit of water applied and mitigate soil salinity that affect a large percentage of irrigated agricultural area in Uzbekistan. Improving efficiency of agricultural water use is a high priority in both countries, particularly since irrigated agriculture provides the food security buffer during severe drought events that affecting both countries.
Expanding the set of experimental tools that U.S. and Uzbek scientists could use to enhance their research efforts. Examples of these tools include transcriptomics and metabolomics, tools for transient expression of microRNAs, and RNAi interference for targeted genome editing and transgenic experiments.
Developing bioinformatics capacity, knowledgeable workforce for efficient analysis of genomic data, and novel training programs to meet workforce needs. Such capacity includes the establishment of high‐performance computer systems.
Addressing global challenges that could adversely affect agriculture, and the environment. An example of such a challenge is climate change, which could affect food production and availability, water availability and quality, and land management.
Preserving Uzbek biodiversity, which is a treasured resource for this nation.
Examining the effects of crop production on the environment and evaluating how environmental changes, including water use and availability, affect crop production.
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Opportunity for Cooperation: Visions of an International Technopark The U.S. and Uzbekistan are exploring the creation of a technopark in Tashkent, Uzbekistan, to build in‐country capacity for biological and biotechnological research, promote scientific exchange, and foster long‐term collaboration between American and Uzbek scientists. The two institutions involved in this project are Texas A&M University (TAMU) from the U.S. and the Center of Genomics and Bioinformatics from Uzbekistan. The technopark would build on past successes in U.S.‐Uzbekistan cooperation on cotton research and initially focus on genomics and bioinformatics. Cooperation could be used to enhance analytic capabilities of bioinformatics data; integrate genetic testing, field studies, and phenotyping; expand laboratory capacity for proteomics, genomics, and phenomics; develop consulting services to help with patenting; establish programs to increase resident expertise in applied research areas – such as agrotechnology and mechanization, water resources management, and integrated pest and disease management – through training and inclusion of consultants.
Studying microbial forensics as a measure to trace pathogen sources in natural or human‐influenced plant disease events and serve as a deterrent. Participants believed that this set of topics might be an appropriate entrée to biosecurity9 concepts in Uzbekistan.
Establishing semi‐industrial or industrial processes to translate scientific results to commercial products. An example could be the commercialization of natural compounds effective at preventing infection of plant pathogens in the laboratory. Another example might be applying research results on efficient water usage in the field with the goal of enabling crop production in areas of limited water supply.
Creating a multi‐institute Uzbek collaborative program that leverages existing capacities and skills (e.g., plant pathology, genomics, disease resistance, breeding, agrotechnology, and irrigation methods) at different research institutions to address new research challenges. These programs could be economical and benefit all involved. The United States has established several of these consortia, such as the Regional Centers of Excellence of the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
Human Health Research The long‐term collaboration opportunities in human health research that were discussed during the sessions can be summarized as follows:
9 The term biosecurity is here defined as the protection from the risks posed by organisms, such as plant pathogens,
to the economy, environment and people’s health
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Conducting research on the microbiome, parasitic worms, and antimicrobial resistance of intestinal pathogens.
Studying genetic diseases, such as high blood pressure, cardiovascular diseases, and hormonal (i.e., endocrine) disorders using population and medical genetic techniques and analyses.
Evaluating identified natural compounds and continuing the search for new active compounds that could prevent or treat diseases, to develop medicinal drugs from selected active compounds.
Conducting advanced cancer research, including a study of genetic differences in drug metabolism among individuals, the development of diagnostics, development of new research models, development of clinical trials for new treatments, and standardization of cancer treatments.
Studying absorption of neutron irradiation (with Gadolinium and Boron) to develop Neutron Capture Therapy for use in cancer patients.
Developing Uzbekistan’s capacity to conduct proteomic studies to examine prevalent diseases, such as gastrointestinal stromal tumors and gastric cancer.
The following figure captures the complex relationships and measurements that link genes with physical and clinical features (the phenotype) (Figure 1). Integration of such diverse information is a major area for training, research, and applications. It is increasingly feasible to start from phenotypes and work toward mechanisms and pathways, and to start from the genes and map them all the way to the phenotypes. While this scheme was developed for human and mammalian studies, it can be applied to all species.
This scheme shows the multiple omics molecular analyses to be integrated with information about environmental exposures, health-related behaviors, physiological measures, and clinical features to link genome and phenome (observable clinical features). Figure from GS Omenn & B Athey, University of Michigan. (scheme reproduced with kind authorization provided by authors)
Scheme first published: Sartor MA, Dolinoy D, Rozek L, Omenn GS. Bioinformatics for high-throughput toxico-epigenomics studies. In Sahu SC (ed), Toxicology and Epigenetics, 1st Ed. Wiley, (Oct 9) 2012, pp.569-588.
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Improving the Process of Cooperation
As workshop participants discussed past collaborative efforts and suggested new opportunities for collaboration, they highlighted several key actions that would build on the strengths of scientists from the United States and Uzbekistan, promote cooperative activities of interest to both countries, enable the acquisition of new research methods or technological advances, ensure development of long‐term cooperative partnerships, and include early‐career scientists in collaborative activities. Based on past successes, participants articulated the following lessons as potential ways to facilitate the development and maintenance of successful international research collaboration:
Select the most appropriate research partner for the defined collaborative effort, and develop joint communication plans, management structures and expectations, and consideration of potential intellectual property and patent rights.
Ensure that the research project is of mutual interest and benefit to both collaborating partners.
o Identify specific areas of research, such as a particular crop species or genetic disease, that affect both the United States and Uzbekistan for which sufficient expertise is present in both countries.
Work jointly with the partner(s) to develop the research design, sample collection methods, analytic processes, and project budgets.
o Ensure that the research questions, experimental design, and data analyses are of high quality to encourage collaboration and facilitate publication in internationally recognized journals.
Identify potential funding opportunities (including grant competitions and/or institutional funds) and prepare grant applications as a team.
o Seek guidance from the funder when trying to identify possible funding opportunities and prepare research proposals.
Provide opportunities for younger scientists to gain new research skills and experience in working with international partners in their area of research interest. These opportunities can derive from the establishment of collaborative projects to encourage future interactions of future generations of scientists as they advance in their fields.
o For example, encourage young computer scientists and mathematicians to work in bioinformatics through collaborative activities between scientists from the United States and Uzbekistan’s Center of Genomics and Bioinformatics.
Consider possible applications and uses of research results and what might be needed to translate basic research to application.
Establish regular face‐to‐face meetings with partners to promote transparent communication and resolve or avoid any challenges that might arise. Once individuals are acquainted, live internet communication can be quite effective and highly cost‐effective to facilitate such communication.
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• Identifying a collaborative partner with shared goals and mutual interests• Determining roles and responsibilities of partners, and developing research plan and project timeline
• Developing a communication plan between partners, which includes in-person meetings
• Identifying potential funder and preparing grant application
Initiating Collaborative Partnerships
• Addressing regulations associated with the research project• Securing the approrpiate approvals to conduct the joint research project• Employing best practices for ethical, social, and legal issues associated with the research project
Conducting Collaborative
Project
• Demonstrating benefits of bilateral research efforts to both countries and potential funders
• Developing a cost-sharing plan between partners and their respective institutions
• Identifying next steps in collaboration, which could include training of young scientists and communication to non-scientists
Building Long-term
Cooperative Partnership
Encourage partners to obtain authoritative statistical and bioinformatics guidance to assist research design and analysis of data, and jointly author articles, publish their results in high impact international journals, and communicate their findings at international conferences.
Keep the overall goal of the research project in mind, whether it is to facilitate economic growth, reduce the prevalence of disease, or understand biological processes at the most fundamental and basic levels.
Critical Steps for Initiating and Maintaining Cooperative Partnerships in the Life Sciences
Challenges and Possible Solutions The most significant challenge participants described was the limited funding; throughout the discussions, participants raised concerns about the availability of financial resources to support bilateral cooperation in the life sciences between the United States and Uzbekistan. Although government agencies, private companies, or disease‐specific philanthropic organizations might support specific areas of research, very few, if any, funding organizations support bilateral cooperation and constructive, positive partnerships between nations. In addition to limited funding opportunities for U.S. ‐ Uzbek scientific cooperation additional challenges were recognized:
High cost of laboratory reagents in Uzbekistan compared to other countries;
Persistent delays in product delivery after purchase.
Time‐consuming process for clearing customs of biological materials imported into Uzbekistan, with a high risk of deterioration of the specimens.
Limited access to service contractors to maintain equipment and facilities.
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Participants suggested possible solutions for addressing these and other challenges. Possible solutions include:
Establishing direct links with supplier companies to minimize difficulties with ordering and receiving laboratory materials.
Providing funds to maintain and upgrade laboratory equipment.
Improving Uzbek scientists’ online access to scientific articles.
Encouraging travel grants and participation in activities of international scientific societies.
Providing language training to facilitate partnership communication and increase chances for project sustainability.
Expediting the customs process in Uzbekistan for delivery of laboratory materials, supplies, and equipment shipped from foreign sources.
Expediting the Uzbek review process for patent filing to avoid losing intellectual property rights on products or other applications of bilateral research activities.
Identifying and addressing any difficulties associated with receiving technology‐specific equipment or software. For example, reducing barriers to receiving software for bioinformatics analyses could help Uzbekistan build their national capabilities for research involving large data sets, such as genomics and proteomics. In addition, common open‐source databases and analytical tools may permit research with large data sets and facilitate collaboration in research projects that involve such data and methods.
Developing clear guidelines for material and resource exchange (i.e., Material Transfer Agreements).
Developing a mechanism for recognition of intellectual property rights for joint projects.
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Appendix A
Workshop Participants
Uzbek Participant List
Acronyms: MAWR ‐ Ministry of Agriculture and Water Resources AS RUz ‐Academy of Sciences of the Republic of Uzbekistan MH ‐ Ministry of Health Note: The following list of Uzbek participant is presented with the following format: Last name, first name Abdullaev Alisher, Ph.D. [email protected] Center of Genomics and Bioinformatics. Head of lab. AS RUz, MAWR, Cotton Industry association Abdurakhmonov Ibrokhim, Ph.D. [email protected] Center of Genomics and Bioinformatics. Director. AS RUz, MAWR, Cotton Industry association Akhunov Alik, Ph.D. [email protected] Institute of Bioorganic Chemistry. Head of lab. AS RUz Aripov Tahir, Ph.D. [email protected]. et Vice President of the Academy of Sciences of Uzbekistan Aripova Tamara, Ph.D. [email protected] Institute of Immunology. Director. AS RUz Asrarov Muzaffar, Ph.D. [email protected] Institute of Bioorganic Chemistry. Head of lab. AS RUz
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Avtonomov Viktor, Ph.D. [email protected], [email protected] Uzbek Research Institute of Cotton Breeding and Seed Growing. Head of lab. MAWR Azimova Shakhnoza, Ph.D. [email protected] Institute chemistry of plant substances named after akad. S. Yu. Yunusov. Head of lab. AS RUz Buriev Zabardast, Ph.D. [email protected] Center of Genomics and Bioinformatics. Deputy Director for Science. AS RUz, MAWR, Cotton Industry association Egamberdiev Sharof, Ph.D. [email protected] Center of Genomics and Bioinformatics. Head of lab. AS RUz, MAWR, Cotton Industry association Eshchanov Ruzimbay, Ph.D. [email protected] Chairman of the Khorezm Mamun Academy, Academy of Sciences of the Republic of Uzbekistan Garib Victoria, Ph.D. [email protected] Tashkent Institute of Post‐Graduate Medical Education. Director of the course for Immunology. Vice Rector for International Cooperation, MH Golubenko Zamira, Ph.D. [email protected] Institute of Bioorganic Chemistry. Senior Scientist. AS RUz Hegay Evgeniya [email protected] Institute of Genetics and Plant Experimental Biology. Head of information‐analytical department. AS RUz Hegay Tatyana, Ph.D. [email protected] Institute of immunology. Head of lab. AS RUz
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Ibadova Gulnara, Ph.D. [email protected] Head of the Chair of Children Infectious and Parasitic Diseases, Tashkent Institute of Post‐Graduated Medical Education, MH Ibragimov Bakhtiyor, Ph.D. [email protected] Academy of Sciences of the Republic of Uzbekistan. General Scientific Secretary. Ibragimov Fazil, Ph.D. [email protected] Institute of Bioorganic Chemistry. Senior Research Associate. AS RUz Ismailov Saidganihodja, Ph.D. [email protected] Republican Specialized Scientific‐Practical Medical Centre of Endocrinology under the Ministry of Health of the Republic of Uzbekistan. Director, MH Ismailova Adolat, Ph.D. [email protected] Institute of immunology. Head of lab. AS RUz Kerimov Fikrat, Ph.D. [email protected] Сentre to scientific technical information Committee for Coordination of Science and Technology Development Republic of Uzbekistan. Director. Khamidova Khurshida, Ph.D. [email protected] Institute of Microbiology, Academy of Sciences of the Republic of Uzbekistan. Director. Khamidullaeva Gulnoz, Ph.D. [email protected] Republican Specialized Center of Cardiology. Head of lab. MH Khaydarova Feruza, Ph.D. [email protected] Republican Specialized Scientific‐Practical Medical Centre of Endocrinology under the Ministry of Health of the Republic of Uzbekistan. Chief of Clinical Department.
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Khodjibaeva Sanabar, Ph.D. [email protected] Institute of Microbiology. Head of lab. AS RUz Kim Andrey, Ph.D. Institute of Nuclear Physics. Senior scientist. AS RUz Koblik Yuriy, Ph.D. [email protected] Institute of Nuclear Physics. Head of lab. AS RUz Marupov Abbaskhon, Ph.D. [email protected] Uzbek Scientific Research Institute of Plant Protection. Head of the Plant Pathology Unit. MAWR Mirzaakhmedov Sharafitdin, Ph.D. [email protected] Education‐Experimental Centre of High Technologies. Head of lab. National University Mukhammedov Rustam, Ph.D. director‐[email protected] Education‐Experimental Centre of High Technologies. Director, National University Mustafina Feruza, Ph.D. [email protected] Institute of Genetics and Plant Experimental Biology. Scientific secretary. AS RUz Namazov Shadman, Ph.D. [email protected] Uzbek Scientific Research Institute of Plant Industry. Director. MAWR Osipova Svetlana, Ph.D. [email protected] Research Institute of Epidemiology, Microbiology and Infectious Diseases. Head of lab. MH Parpiev Odilkhuja, Ph.D. Committee for coordination science and technology development under Cabinet of Ministers of Uzbekistan. Head of Executive Office.
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Perimkulova Vasila, Ph.D. [email protected] Head of Department of Foreign Relations Academy of Sciences of the Republic of Uzbekistan Rashidova Sayyora, Ph.D. [email protected] Institute of Chemistry and Physics of Polymers. Director. AS RUz Sabirov Ravshan, Ph.D. [email protected] National University of Uzbekistan Sagdiyev Nail, Ph.D. [email protected] Institute of Bioorganic Chemistry. Head of lab. AS RUz Sagdullaev Shamansur, Ph.D. [email protected], [email protected] Institute of Chemistry of Plant Substances. Director. AS RUz Salikhov Shavkat, Ph.D. [email protected] President of the Academy of Sciences of the Republic of Uzbekistan Shermatov Shukhrat, Ph.D. [email protected] Center of Genomics and Bioinformatics. Scientific Secretary. AS RUz, MAWR, Cotton Industry association Syrov Vladimir, Ph.D. [email protected] Institute of Chemistry of Plant Substances. Head of department. AS RUz Tashpulatov Javlon, Ph.D. [email protected] Institute of Microbiology, AS RUz
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Tukhtaev Bobokul, Ph.D. [email protected] Institute of Gene Pool of Plants and Animals. Director. AS RUz Turaev Abbaskhan , Ph.D. [email protected] Institute of Bioorganic Chemistry. Director. AS RUz Turdieva Muhabbat, Ph.D. [email protected] Bioversity International sub‐regional office for Central Asia. Regional Project Coordinator. Turdikulova Shahlo, Ph.D. [email protected] Education‐Experimental Centre of High Technologies. Chief of the Biology Department. National University Usmanov Rustam, Ph.D. [email protected] Institute of Genetics and Plant Experimental Biology. Director. AS RUz Veshkurova Olga, Ph.D. [email protected] Institute of Bioorganic Chemistry. Head of lab. AS RUz Yakubov Iskandar, Ph.D. [email protected] Institute of Bioorganic Chemistry. Senior Scientist. AS RUz
U.S. Participant List Caylor Kelly K., Ph.D. [email protected] Environmental Sciences, Assistant Professor Department of Civil and Environmental Engineering, Princeton University
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Coat Gwenaële, M.Sc. [email protected] Senior Program Associate International Office American Association for the Advancement of Science Evett Steven R., Ph.D. [email protected] Research Soil Scientist and Lead Scientist USDA Agricultural Research Service, Conservation & Production Research Laboratory Farnsworth Rayna Pol/Econ Officer, U.S. Embassy in Tashkent Fletcher Jacqueline, Ph.D. [email protected] Regents Professor, Department of Entomology and Plant Pathology, Oklahoma State University The Honorable Krol George U.S. Ambassador to the Republic of Uzbekistan Mukhamadiev Bakhtiyor Scientific Affairs Specialist, U.S. Embassy in Tashkent Neureiter Norman P., Ph.D. [email protected] Senior Advisor, Acting Director Center for Science Diplomacy and Center for Science, Technology and Security Policy American Association for the Advancement of Science Omenn Gilbert S., M.D., PhD [email protected] Director of Center for Computational Medicine and Bioinformatics Professor of Internal Medicine, Human Genetics, and Public Health University of Michigan Pepper Alan, Ph.D. [email protected] Associate Professor Texas A&M University
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Robinson Chris [email protected] Director, Cooperative Research Program CRDF Global Saha Sukumar, Ph.D. [email protected] Research Geneticist USDA Agricultural Research Service Scheffler Jodi, Ph.D. [email protected] Cotton Geneticist USDA Agricultural Research Service Schwartz Robert C., Ph.D. [email protected] Research Soil Scientist USDA Agricultural Research Service Silva Joseph, M.D, M.A.C.P [email protected] Professor of Internal Medicine, Dean Emeritus UC Davis School of Medicine Stipanovic Robert, Ph.D. [email protected] Research Geneticist, Supervisory Research Chemist USDA Agricultural Research Service Stelly David, Ph.D. [email protected] Professor, Department of Soil & Crop Sciences Texas A&M University Ulloa Mauricio, Ph.D. [email protected] Research Geneticist USDA Agricultural Research Service
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Verma Inder, Ph.D. [email protected] Professor, Laboratory of Genetics Irwin and Joan Jacobs Chair in Exemplary Life Science Ward Joy, Ph.D. [email protected] Associate Professor University of Kansas Yuldashbaev Nizam USDA/FAS Agricultural Specialist, U.S. Embassy in Tashkent
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Appendix B
Workshop Agenda
Uzbekistan ‐ U.S. Life Sciences Collaboration: Defining the Opportunities September 27‐29, 2012 Tashkent, Uzbekistan
Meeting Agenda
September 26: 20:00 Welcome Dinner for American Scientists (Hotel) September 27: Priorities and Structure of Science in the Republic of Uzbekistan (UZB) and the U.S. 9:00‐ 9:30 Registration 9:30‐10:00 Welcome and Meeting Goals 9:30‐9:40 Shavkat Salikhov, President of the Academy of Sciences of the Republic of Uzbekistan (AS RUz) 9:40‐9:50 Norman Neureiter, AAAS 9:50‐10:00 His Excellency Krol George, U.S. Ambassador to the Republic of Uzbekistan 10:00‐10:45 Description of Scientific Research and Education System in Republic of Uzbekistan
10:00‐10:15 Odilkhuja Parpiev, Committee for coordination science and technology development
10:15‐10:30 Omenn Gilbert S., University of Michigan «The Organization and Conduct of Scientific Research in America» 10:30‐10:45 Bakhtior Ibragimov, Academy of Sciences of the Republic of Uzbekistan
10:45‐11:15 Example of successful collaboration – part 1
10:45‐11:00 Ibrokhim Abdurakhmonov, Center of Genomics and Bioinformatics, AS RUz, MAWR, Cotton Industry association
11:00‐11:15 Alan E. Pepper, Texas A&M University (TAMU) 11:15‐11:45 Coffee break 11:45‐12:15 Example of successful collaboration – part 2 11:45‐12:00 Olga Veshkurova, Institute of Bioorganic Chemistry Laboratory, AS RUz 12:00‐12:15 Robert Stipanovic, USDA/ARS 12:15‐13:45 Lunch
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13:45‐14:30 Free time for Posters 14:30‐16:00 Scientific Presentations
American and Uzbek scientists will give 15‐minute presentations on their research expertise in broad terms.
SESSION 1. HUMAN HEALTH
Chairman Gilbert Omenn, CCMB, University of Michigan Co‐Chairman Tatyana Hegay, Institute of immunology, AS RUz
14:30‐14:45 Shakhnoza Azimova, Institute chemistry of plant substances «Biotechnology for Pharmaceutical Products». 14:45‐15:00 Joseph Silva, University of California, Davis ‐ School of Medicine «Biomedical Research at University of California, Davis ‐ One Health» 15:00‐15:15 Glunara Ibadova, Tashkent Institute of Post‐Graduated Medical
Education, MH «Detection of integrons, sequencing and identification of genes for
reveling of resistance mechanisms for antibacterial medications in intestinal pathogens».
15:15‐15:30 Inder Verma, Laboratory of Genetics «Cancer: Malady of Genes» 15:30‐15:45 Iskandar Yakubov, Institute of Bioorganic Chemistry, AS RUz «Physiological genomics of gastric parietal and ecl cells» 15:45‐16:00 Yuriy Koblik, Institute of Nuclear Physics, AS RUz
Development of neutron‐trapping therapy in Uzbekistan»
16:00‐16:30 Coffee break 16:30‐18:00 SESSION 2. AGRICULTURE & ENVIRONMENT
Chairman Jacqueline Fletcher, Oklahoma State University Co‐Chairman Alik Akhunov, Institute of Bioorganic Chemistry
16:30‐16:45 Sukumar Saha, USDA/ARS «Advances in Cotton genomics» 16:45‐17:00 Alik Akhunov, Institute of Bioorganic Chemistry «Anionic peroxidase isoforms as indicators of cotton Verticillium wilt
resistance» 17:00‐17:15 Kelly Caylor, Department of Civil and Environmental Engineering, Princeton University «Water for Sustainable Ecosystems» 17:15‐17:30 Ibrokhim Abdurakhmonov, Center of Genomics and Bioinformatics «RNAi technology for improvement of cotton fiber quality and other
agronomic traits» 17:30‐17:45 Joy Ward, University of Kansas «Climate Change and Plants: Preparing for the Future» 17:45‐18:00 Brad Haley, USDA/ARS – Canceled
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«Genomic and Metagenomic Analyses of Pathogens in the Bovine Intestine»
19:00‐21:00 Dinner Sept 28: Exploring areas of cooperation in Human and Animal Health and Agriculture and Environmental Sciences 9:00‐9:15 Meeting format and desired outcomes 9:15‐12:15 Breakout sessions on new scientific development Breakout session 1: Human Health Chairman Azimova Shakhnoza, Institute chemistry of plant substances Co‐Chairman Joseph Silva, UC Davis School of Medicine Rapporteurs Chris Robinson, CRDF Global
09:15‐09:30 Mukhamedov «Studies of mtDNA composition of Uzbekistan and currents of medical genetics» 09:30‐09:45 Gilbert Omenn, University of Michigan «Medical Research Based on 'Omics Technologies and Opportunities for International
Collaboration» 09:45‐10:00 Svetlana Osipova, Research Institute of Epidemiology, Microbiology and Infectious
Diseases «Role of intestinal parasites and protists fauna in pathogenesis of allergic diseases,
inflammatory bowel diseases. Their influence on health of high rank sportsmen and methods of correction»
10:00‐10:15 Gulnoz Khamidullaeva, Republican Specialized Center of Cardiology «M235T polymorphism of AGT gene and cardio‐vascular remodeling processes in
hypertension». 10:15‐10:30 Fazil Ibragimov, Institute of Bioorganic Chemistry
«Изучение биологической активности белкового препарата из сои в лечении онкологических заболеваний»
10:30‐11:00 Coffee break 11:00‐11:15 Shamansur Sagdullaev, Institute of Chemistry of Plant Substances «The contribution of the chemistry of natural substances to medicine and agriculture of
Uzbekistan» 11:15‐11:30 Nail Sagdiyev, Institute of Bioorganic Chemistry «Isolation, primary structure determination and cloning of the gene of the insectotoxin
bucait from the caucasian subspecies of scorpion Mesobuthus caucasicus». 11:30‐12:00 Discussion in breakout session
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Breakout session 2: Agriculture and Environmental Sciences Chairman Alan Pepper, TAMU Co‐Chairman Ibrokhim Abdurakhmonov, Center of Genomics and Bioinformatics Rapporteurs Jodi Scheffler, USDA
09:15‐09:30 Olga Veshkurova, Institute of Bioorganic Chemistry «Terpenoids and antimicrobial peptides from central asian plants. Modes of mechanism, modulation of defense responses»
09:30‐09:45 Jacqueline Fletcher, Oklahoma State University «Research Synergies at the Intersections of Plant Pathology, Food Safety, Forensic Science and Agricultural Biosecurity»
09:45‐10:00 Zabardast Buriev, Center of Genomics and Bioinformatics «Molecular evolution of clustered MIC‐3 (Meloidogyne Induced Cotton‐3) multigene family of Gossipium species»
10:00‐10:15 David Stelly, TAMU «Genomic, chromosomal and genetic manipulations for cotton genetic research and improvement»
10:15‐10:30 Sanabar Khodjibaeva, Institute of Microbiology «New strategy of development of microbial preparations for biocontrol of verticillum wilt in cotton»
10:30‐11:00 Coffee break 11:00‐11:15 Steve Evett, USDA «Irrigation Science and Water Quality Challenges in Uzbekistan» 11:15‐11:30 Alisher Abdullaev A. , Center of Genomics and Bioinformatics «Current studies of Uzbek cotton germplasm collection» 11:30‐12:00 Discussion in breakout session 12:15‐13:45 Lunch 13:45‐14:30 Poster Session 14:30‐16:30 Breakout sessions on new scientific development Breakout session 1: Human & Animal Health Chairman Inder Verma, Laboratory of Genetics, Salk Institute Co‐Chairman Saidganihodja Ismailov, Republican Specialized Scientific‐Practical Medical Centre of Endocrinology Rapporteurs Kelly Caylor, Princeton University 14:30‐14:45 Vladimir Syrov, Institute of Chemistry of Plant Substances «Advisability of application of preparations with adaptogenic, immunomodulating and
antiparasitic activity, isolated from endemnic plants of Uzbekistan, for sanitation living under unfavorable ecologic conditions»
14:45‐15:00 Saidganihodja Ismailov, Republican Specialized Scientific‐Practical Medical Centre of Endocrinology
«Molecular‐Genetic Researches in Endocrinology». 15:00‐15:15 Shahlo Turdikulova, Education‐Experimental Centre of High Technologies
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«The role of N‐glycosilation in trafficking and sorting of membrane glycoproteins in epithelial cells»
15:15‐15:30 Tatyana Hegay, Institute of immunology «The multilocus genetic Landscape of central Asia: reality and dreams» 15:30‐15:45 Muzaffar Asrarov, Institute of Bioorganic Chemistry «Influence of salvipholin on rat liver mitochondrial permeability transition pore under
alloxan diabetes». 15:45‐16:30 Discussion in breakout session Breakout session 2: Agriculture and Environmental Sciences Chairman Joy Ward, University of Kansas Co‐Chairman Ruzimbay Eshchanov, Khorezm Mamun Academy Rapporteurs Steve Evett, USDA 14:30‐14:45 Robert Schwartz, USDA «Optimizing the use of limited water in agricultural systems» 14:45‐15:00 Abbaskhon Marupov, Uzbek Scientific Research Institute of Plant Protection «Cotton wilt disease in Uzbekistan» 15:00‐15:15 Mauricio Ulloa, USDA «Improving Disease Resistance in the Cotton Crop» 15:15‐15:30 Sharof Egamberdiev, Center of Genomics and Bioinformatics «Molecular detection of Fusarium oxysporum f. sp. vasinfectum (FOV) in cotton» 15:30‐15:45 Jodi Scheffler, USDA «Accelerating breeding progress, combining classical breeding methods with new
biotechnology techniques» 15:45‐16:30 Discussion in small group 16:30‐17:00 Coffee break 17:00 – 18:00 Discussion and Wrap‐Up of two break‐out sessions in one group Rapporteurs to present a short report on each break out. Discussion leaders: Shavkat Salikhov, AS RUz Norman Neureiter, AAAS 19:00‐21:00 Dinner September 29: Meeting wrap up and future plans– Laboratory visits 9:00‐12:30 Topic Three: Key elements for successful collaboration
Chairman Norman Neureiter, AAAS Co‐Chairman Bakhtiyor Ibragimov, AS RUz Rapporteurs Robert Stipanovic, USDA 9:00‐9:15 Sayyora Rashidova, Institute of polymer chemistry 9:15‐9:30 Chris Robinson, CRDF Global
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«Successful International Cooperation: A Funder's Perspective» 9:30‐9:45 Khurshida Khamidova, Institute of Microbiology «Development of microbial biotechnology at the institute of
microbiology» 9:45‐10:00 Joseph Silva, UC Davis School of Medicine 10:00‐10:15 Bobokul Tukhtaev, Institute of Gene Pool of Plants and Animals «Flora and fauna of Uzbekistan» 10:15‐10:30 Rustam Usmanov, Institute of Genetics and Plant Experimental Biology «Priorities and perspectives for development of the scientific research at
the Institute of genetics and plants experimental biology» 10:30‐10:45 Inder Verma, Laboratory of Genetics, Salk Institute
10:45‐11:00 Coffee break
11:00‐11:15 Abbaskhan Turaev, Institute of Bioorganic Chemistry 11:15‐12:15 Discussion in one big group
12:15‐13:00 Summary of entire meeting – all together
Norman Neureiter, AAAS Shavkat Salikhov, AS RUz Open floor for discussion of the outcomes of the meeting and plans for the next meeting in the United States of America.
13:00‐14:00 Lunch 14:00‐16:30 Lab Visits:
Location 1: Center of Genomics and bioinformatics, AS RUz: laboratory and field station (Iborkhim Abdurakhmonov) Location 2: Laboratory for biological diagnostics tools Institute of Nuclear physics, AS RUz (U. Salikhboev); Location 3: Medical center (to be confirmed)
16:30 Adjourn
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Appendix C
Research in Environmental and Agricultural Sciences
Workshop participants included scientists who engaged in cooperative research on cotton, scientists with expertise in water management, plant pathology and biosecurity, and climate change. The resulting discussion involved lessons learned from the past collaborations on cotton research and possible cooperative opportunities for research on other crops of interest to Uzbekistan. Cooperative research efforts on cotton involved scientists from the U.S. Department of Agriculture (USDA) Agricultural Research Service (ARS), Texas A&M University, and several Uzbek institutes (Academy of Science of Uzbekistan, Center of Genomics and Bioinformatics, Institute of Genetics and Plant Experimental Biology, Institute of Gene Pool of Plants and Animals, Uzbek Research Institute of Cotton Breeding and Seed Growing, Uzbek Scientific Research Institute of Plant Industry, Uzbek Scientific Research Institute of Plant Protection). Lessons from the bilateral cooperation on cotton research could inform future cooperative research efforts on non‐cotton crops in which Uzbekistan is investing.
Cotton Research
During the AAAS‐AS RUz workshop, scientists described many of the cooperative research activities with cotton, which focused primarily on reducing the impact of plant diseases, characterizing cotton varieties using genomic analyses, and improving the efficiency of irrigation for cotton. Participants built on these successful research projects to identify new opportunities for cooperation. The following list describes examples of current or past research activities on cotton presented at the meeting by U.S. and Uzbek scientists: 1. Plant disease studies:
Control of pathogens using natural compounds.
Identification of new, aggressive strains of pathogens that cause disease in cotton plants and result in reduced cotton yields.
Association of cotton enzymes with resistance to plant pathogens. 2. Genomic research to improve the cotton varieties:
Disease resistance: o Molecular characterization and identification of high priority strains of fungal
plant pathogens. o Control of fungal pathogens of cotton using genomic technologies and RNA
interference.
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o Development of cotton breeding techniques. o Identification of fungal resistance in cotton germplasm collections. o Assessment of the use of genetic elements to develop heartier cotton crops using
genetic modification.
Crop productivity, fiber quality, and environmental tolerance (temperature, drought, and salt):
o Development of cotton plants with unique seed properties to be used in animal feed.
o Use of quantitative trait locus mapping to identify genetic traits associated with fiber quality.
o Use of RNA interference to develop transgenic cotton plants with improved fiber quality.
o Study of cotton genes in the Arabidopsis thaliana plant research model system. o Use genetic technologies to enhance commercially available cotton varieties. o Development of an assay to identify cotton strains.
Agricultural and Environmental Research beyond Cotton Research The following list describes examples of current or past research activities on Agricultural and Environmental Research presented at the meeting by U.S. and Uzbek scientists: 1. Enhancement of water usage:
Improvement of irrigation methods, water management, and tillage practices to increase crop production.
Use of isotopic techniques to measure water use efficiency and fertilizer practices10;
Improvement of water management and usage for multiple crops, including winter wheat, maize, and mung bean.
Water quality study for ecosystems and human health.
Use of excavation methods and ground‐penetrating radar to map soil carbon and root structures in drought conditions.
Study of social and environmental aspects of hydrological change.
Monitoring of the water cycle, drought, and crop production in dry lands.
Forecast studies of drought and crop production. 2. Study of the effects of climate change on crops:
Examination of increased carbon dioxide levels on flowering time.
Assessment of the effects of different environmental conditions, such as carbon dioxide levels and temperatures on plants.
3. Introduce new areas of research on plant pathology, food safety, plant forensic science, and agricultural biosecurity11:
10 Isotopic techniques are used to gather data on soil, water and plants, which in turn can be used to recommend
water irrigation and fertilization amounts to improve crop production, preventing soil degradation for enhanced agricultural management practices.
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Control of naturally or intentionally released plant pathogens, pests, and weeds of food crops:
o Development and validation of robust diagnostic tools to identify natural or human‐influenced plant disease in crops. Examples of diagnostic tools: Next generation sequencing for agricultural bioforensics. Novel polymerase chain reaction (PCR) design. Assays for identifying waterborne pathogens. Assays for discrimination of plant pathogen strains. Field deployable PCR tests. Bioinformatic tools.
o Examination of pathogens that infect both plants and humans, and enteric pathogens that contaminate fresh plant‐based foods.
11 Biosecurity here also means the action to protect crops and livestock from the risks posed by organisms
(viral, bacterial, fungal, or parasitic) to the agriculture, economy, environment and people’s health
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Appendix D
Research in Human Health Sciences
Genetic disorders and other related human diseases are significant concerns in Uzbekistan. Scientists from the following institutions in Uzbekistan presented some of their activities from which cooperative opportunities might arise. The centers and institutions were: Academy of Sciences of Uzbekistan, including the Institute of Chemistry of Plant Substances, Institute of Bioorganic Chemistry, Institute of Immunology, Institute of Microbiology, and Institute of Nuclear Physics; the National University’s Education‐Experimental Centre of High Technologies; and the Ministry of Health, including the Tashkent Institute of Post‐Graduated Medical Education, Republican Specialized Center of Cardiology, Republican Specialized Scientific‐Practical Medical Centre of Endocrinology, Research Institute of Epidemiology, and Microbiology and Infectious Diseases. The following lists describes the research on human health, including research on cancer and infectious diseases, that were presented at the meeting.
Research on Bioactive Substances and Compounds Isolation, identification, and cloning of the insectotoxin gene from a Caucasian
subspecies of scorpion. The potential use for the gene product could be cancer treatment.
Examination of the chemical composition and therapeutic uses of bentonite clays.
Assessment of the biological activity of the soybean protein. The soybean protein might be used as cancer therapy.
Examination of the effects of plant compounds in preventing or treating diabetes under experimental conditions.
Identification of recombinant vaccines from insects or worms that could prevent Hepatitis B infection.
Development of a diagnostic method that uses poisonous snake venom for early diagnosis of heart disease.
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Research using Emerging Technologies Characterization of hereditary diseases in the Uzbek population using mitochondrial
DNA analysis.
Study of the gastric cells and glands using physiological genomic analyses.
Genetic and endocrinology studies of Turner syndrome and diabetes.
Study of infectious diseases, gastric cancer, breast cancer, and ovarian cancer using genomic technologies.
Examination of the adenomatous polyposis of colon and rectal cancers.
Study of the genetic determinants of hypertension.
Development of methods to diagnose inherited and multi‐factorial diseases.
Assessment of pathogen antibiotic resistance on intestinal pathogens.
Neutron Capture Therapy for cancer studies.
Characterization of the all human proteins and their different forms, and contribution to the Human Proteome Project12.
Characterization of proteins that contribute to tumor growth and metastasis.
12 http://www.hupo.org/research/hpp/; Central Asian J Global Health, 2012