Malaria Research Institute

Cape Saint Claire, MD, United States

Malaria Research Institute

Cape Saint Claire, MD, United States
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News Article | February 28, 2017

From eradicating weapons of mass destruction to the scourge of malaria, speakers at a UA conference -- including a Nobel laureate, ambassadors and advisers to secretaries of state -- know firsthand how science can build trust where politics cannot In times of diplomatic turmoil and combative negotiations, scientists and engineers will continue solving problems and seeking the truth, speakers affirmed at a recent University of Arizona summit on science diplomacy and policy. "When others deny climate change, ask for the evidence," said Norman Neureiter, a former staff member in the White House Office of Science and Technology and the first science and technology adviser to a secretary of state. "It is scientific evidence that is essential for setting sound policies. Science is how we know the truth, how we understand the natural world. It is not an ideology." Neureiter was involved as an interpreter in private discussions with scientists on nuclear weapons testing with the former Soviet Union in the 1960s and as a participant in semiconductor negotiations with Japan in the late 1980s. Scientists and engineers played a critical role in reaching final agreements, he said. Neureiter spoke at a panel on February 21 to kick off the conference, which focused on climate change and water sustainability in the Americas. The conference was co-sponsored by the UA College of Engineering, Office of Global Initiatives and other programs and chaired by Kevin Lansey, head of the UA Department of Civil Engineering and Engineering Mechanics. More than 130 students, scientists, engineers, foreign diplomats and local residents attended the panel at the Tucson Marriott University Park. "We have a responsibility to share our knowledge with people in countries throughout the world, whatever our diplomatic relationships may be," said Peter Agre, recipient of the Nobel Prize in chemistry. He has led scientific delegations to Cuba, North Korea, Iran and other countries that have strained or nonexistent diplomatic relations with the U.S. Agre, director of the Malaria Research Institute at Johns Hopkins University Bloomberg School of Public Health, shared stories and slides from his research programs to eradicate malaria in the Democratic Republic of Congo, Zimbabwe and other African nations with authoritarian regimes. "These countries are rich in terms of minerals, but they bear a staggering burden from malaria, which kills approximately 400,000 children each year worldwide," he said. He offered a rare glimpse inside North Korea, which he has visited three times as the head of AAAS delegations to teach students, meet scientists and facilitate research collaborations at Pyongyang University of Science and Technology. "We shared stories about our research and hopes for our children and our grandchildren," said the former president of the American Association for the Advancement of Science. "Friendships can make a difference." Agre met with Fidel Castro as head of a U.S. scientific delegation to Cuba in 2011. "There were obviously many things we disagreed on," he said, "but Castro understood that science would play an important role in advancing Cuba's economy and lifting its people. That was one thing we could agree on." In 2012 he led a AAAS delegation to Iran. "Overall, it was a very positive visit," Agre said in an article for AAAS. "Our meetings with faculty and students were always positive -- it seems to me that we all have a lot to share.... From a scientific viewpoint, the doors are certainly open." When tensions did arise, the delegates focused on constructive science engagement. "We weren't there to apologize or criticize; we were there to talk about science and to find common ground," he said. Thomas R. Pickering, vice chairman of a consulting company and former U.S. ambassador to seven countries -- including the Russian Federation and Israel -- and the United Nations, had to cancel his planned trip to Tucson to participate in the panel. So his address about his storied career spanning six decades was delivered via video. In introducing him, E. William Colglazier, a former science and technology adviser to secretaries of state Hillary Clinton and John Kerry and the honorary chairman of the UA conference, called Pickering the "premier and most well-connected American ambassador of our time." Pickering, a participant in some of the most consequential diplomatic developments of the 20th and 21st centuries, considers the Iran nuclear agreement an important contribution to science diplomacy. "This agreement might become the international gold standard for reaching agreements with developing nations," he said. "It calls for surveillance from uranium mining extraction to disposal of spent fuel rods and ensures 24/7 knowledge of what is happening in the Iran nuclear program. It highlights the need for acceptance to compromise, on both sides, and could be an important guide for future negotiations with developing countries." "It is incredible for undergraduate students to be able to interact with such important scientists and policy experts," said Estefanie Govea, who has a UA bachelor's degree in political science and is pursuing a second bachelor's in environmental and water resource economics in the College of Agriculture and Life Sciences. "Unless you are well-connected, most undergraduates miss out on great opportunities like this." She is one of several UA students, most in the College of Engineering, who served as rapporteurs and will write conference proceedings to be submitted in the AAAS journal Science & Diplomacy and ensure that all conference presentations are posted online. During the Wednesday evening panel Q&A, speakers expressed apprehension about how the Trump administration's travel bans and proposed budget cuts might hamper scientific research and innovation. "America up until now has been a haven for thousands of scientists and scholars who have come to the U.S. to escape persecution and conflict elsewhere," said Neureiter, an adviser at AAAS. "They have made huge contributions to America's technical and scientific excellence." He added, "I have serious concerns about threatened cuts in various government department budgets. America must not fall behind in scientific research, engineering and innovation. These disciplines are vital for the future growth of the U.S. economy and for the health and well-being of the American people."

Wang S.,CAS Shanghai Institutes for Biological Sciences | Jacobs-Lorena M.,Malaria Research Institute
Trends in Biotechnology | Year: 2013

Malaria remains one of the most devastating diseases worldwide, causing over 1 million deaths every year. The most vulnerable stages of Plasmodium development in the vector mosquito occur in the midgut lumen, making the midgut a prime target for intervention. Mosquito transgenesis and paratransgenesis are two novel strategies that aim at rendering the vector incapable of sustaining Plasmodium development. Mosquito transgenesis involves direct genetic engineering of the mosquito itself for delivery of anti-. Plasmodium effector molecules. Conversely, paratransgenesis involves the genetic modification of mosquito symbionts for expression of anti-pathogen effector molecules. Here we consider both genetic manipulation strategies for rendering mosquitoes refractory to Plasmodium infection, and discuss challenges for the translation of laboratory findings to field applications. © 2013 Elsevier Ltd.

Smith R.C.,Malaria Research Institute | Vega-Rodriguez J.,Malaria Research Institute | Jacobs-Lorena M.,Malaria Research Institute
Memorias do Instituto Oswaldo Cruz | Year: 2014

Nearly one million people are killed every year by the malaria parasite Plasmodium. Although the disease-causing forms of the parasite exist only in the human blood, mosquitoes of the genus Anopheles are the obligate vector for transmission. Here, we review the parasite life cycle in the vector and highlight the human and mosquito contributions that limit malaria parasite development in the mosquito host. We address parasite killing in its mosquito host and bottlenecks in parasite numbers that might guide intervention strategies to prevent transmission.

Stresman G.H.,Malaria Research Institute
Acta Tropica | Year: 2010

Being able to identify the ecological factors that impact risk for malaria would confer important predictive capacity to target malaria control interventions in a community. Temperature and water available for breeding habitats have been shown to be important primary ecological factors that impact the distribution of the malaria vectors and the rate at which the mosquito and parasite develop. However, to this point, studies focusing on the local level have been met with many inconsistent results when assessing malaria risk using both temperature and precipitation. This paper reviewed existing literature to determine if other ecological factors beyond temperature and water are present that may be modifying any associations present between ecological factors and malaria risk. It was found that the ability for water to pool and persist, water quality, elevation, deforestation, and agriculture have all been associated with malaria and may be modifying risk. Using the primary and modifying ecological variables, identifying the interactions between these factors and specific thresholds for increased malaria risk is critical: filling this knowledge gap would enable communities to develop tailored malaria control interventions targeted to their specific circumstances. © 2010 Elsevier B.V.

Sullivan D.,Malaria Research Institute
Epidemiologic Reviews | Year: 2010

Malaria is a location-specific, dynamic infectious disease transmitted by mosquitoes to humans and is influenced by environmental, vector, parasite, and host factors. The principal purposes of malarial epidemiology are 1) to describe the malarial distribution in space and time along with the physical, biologic, and social etiologic factors and 2) to guide control objectives for either modeling impact or measuring progress of control tactics. Mapping malaria and many of its causative factors has been achieved on many different levels from global distribution to biologic quantitative trait localization in humans, parasites, and mosquitoes. Despite these important achievements, a large degree of uncertainty still exists on the annual burden of malarial cases. Accurate, sensitive detection and treatment of asymptomatic reservoirs important to infectious transmission are additional components necessary for future control measures. Presently spurred by the leadership and funding of Bill and Melinda Gates, the malarial community is developing and implementing plans for elimination of malaria. The challenge for malariologists is to digitally integrate and map epidemiologic factors and intervention measures in space and time to target effective, sustainable control alongside research efforts. © 2010 The Author.

Ramirez J.L.,Malaria Research Institute | Dimopoulos G.,Malaria Research Institute
Developmental and Comparative Immunology | Year: 2010

Dengue virus has become one of the most important arboviral pathogens affecting the world today. The virus is transmitted among humans by the mosquitoes Aedes aegypti and Ae. albopictus. Like other vector-borne pathogens, this virus encounters innate immune defenses within the mosquito vector that limit infection. We have previously demonstrated the involvement of the Toll pathway in the anti-dengue defense at 7 days after infection. In the present study, we have investigated the activity of this immune signaling pathway against different dengue virus serotypes at the early stages of infection in laboratory and field-derived mosquito strains. Our studies corroborate the importance of the Toll pathway in the anti-dengue defense repertoire at 3 days after an infectious blood meal, when new virions are released from the midgut for dissemination and infection of other mosquito tissues. These immune defenses are furthermore conserved among different Ae. aegypti strains and can act against a broad range of dengue virus serotypes. © 2010 Elsevier Ltd. All rights reserved.

McLean K.J.,Malaria Research Institute | Jacobs-Lorena M.,Malaria Research Institute
Trends in Parasitology | Year: 2016

Experiments demonstrating the feasibility of genetically modifying mosquito vectors to impair their ability to transmit the malaria parasite have been known for well over a decade. However, means to spread resistance or population control genes into wild mosquito populations remains an unsolved challenge. Two recent reports give hope that CRISPR technology may allow such challenge to be overcome. © 2016 Elsevier Ltd.

Spalding M.D.,Malaria Research Institute | Prigge S.T.,Malaria Research Institute
Microbiology and Molecular Biology Reviews | Year: 2010

Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Ghosh A.K.,Malaria Research Institute | Jacobs-Lorena M.,Malaria Research Institute
Memorias do Instituto Oswaldo Cruz | Year: 2011

Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential, especially for organisms devoid of the Krebs cycle that depend solely on glycolysis for energy. Interestingly, enolase appears to serve a separate function in some organisms, in that it is also exported to the cell surface via a poorly understood mechanism. In these organisms, surface enolase assists in the invasion of their host cells by binding plasminogen, an abundant plasma protease precursor. Binding is mediated by the interaction between a lysine motif of enolase with Kringle domains of plasminogen. The bound plasminogen is then cleaved by specific proteases to generate active plasmin. Plasmin is a potent serine protease that is thought to function in the degradation of the extracellular matrix surrounding the targeted host cell, thereby facilitating pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also expresses surface enolase, and that this feature may be essential for completion of its life cycle. The therapeutic potential of targeting surface enolases of pathogens is discussed.

Sinnis P.,Malaria Research Institute | Zavala F.,Malaria Research Institute
Seminars in Immunopathology | Year: 2012

Infection by malaria parasites begins with the inoculation of sporozoites into the skin of the host. The early events following sporozoite deposition in the dermis are critical for both the establishment of malaria infection and for the induction of protective immune responses. The initial sporozoite inoculum is generally low, and only a small percentage of these sporozoites successfully reach the liver and grow to the next life cycle stage, making this a significant bottleneck for the parasite. Recent studies highlight the importance of sporozoite motility and host cell traversal in dermal exit. Importantly, protective immune responses against sporozoites and liver stages of Plasmodium are induced by dendritic cells in the lymph node draining the skin inoculation site. The cellular, molecular, and immunological events that occur in the skin and associated lymph nodes are the topic of this review. © 2012 Springer-Verlag Berlin Heidelberg.

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