National Research Foundation

SAN DIEGO, June 26, 2024 /PRNewswire/ -- The 2024 BIO International Convention, the world's largest biotechnology event, took place in San Diego, USA, from June 3 to 6. This year's convention drew biomedical investors and research experts worldwide. Over 1,500 exhibitors showcased their innovations to more than 19,500 attendees from 70 countries. The Taiwan Pavilion garnered significant attention, holding over 400 meetings in four days and highlighting Taiwan's rising biotech industry. Leading Taiwanese Pharmaceutical Companies' Capabilities Showcased Continue Reading Taiwan's Biotech Innovations Draw International Attention at BIO 2024, source: GeneOnline. The 2024 BIO International Convention's theme was "Time for Science to Shine." The Taiwan delegation, organized by the Ministry of Economic Affairs (MOEA) Biotechnology and Pharmaceutical Industries Promotion Office (BPIPO), in collaboration with the Ministry of Health and Welfare, Ministry of Agriculture, National Science and Technology Council, National Development Council, Taipei City Government, and the National Biotechnology Research Park. The delegation included over 80 companies and institutions, with around 230 participants. The delegation focused on new drug development, biotechnology, CDMO (Contract Development and Manufacturing Organization), medical devices, precision medicine, regenerative medicine, agricultural biotechnology, and smart health. International buyers showed strong interest in cancer treatment and CDMO, indicating significant investment potential. The Taiwan Pavilion featured a CDMO wall showcasing 10 leading Taiwanese pharmaceutical companies' capabilities. This display highlighted Taiwan's strengths in intellectual property, regulatory frameworks, and policy support, positioning Taiwan as an ideal partner for international technical and manufacturing collaborations. Taiwan Pavilion Highlights Pharma Prowess To strengthen international connections, the Taiwan Pavilion hosted an opening reception and co-organized thematic conferences on cell/gene therapy processes in the Asia-Pacific region and smart innovation digital applications. These efforts aimed to accelerate industry development and foster global integration. The Taiwan Pavilion's exhibits featured new drug development projects, including botanical drugs, small molecule drugs, and protein drugs at various stages. They also showcased delivery systems, personalized tumor avatars, organ-on-a-chip technology, universal antibody platforms, cell therapy, and cell culture technologies. Precision and smart medical solutions were highlighted, such as interactive medical 3D imaging, cancer diagnostics, AI physiological monitoring, rapid screening for high-risk neurological diseases, targeted cancer therapies, adhesive patch technology, early cancer screening, and 3D pathological imaging. Taiwan's biotech startups also shone on the international stage, with five companies reaching the final round of the BIO Start-Up Stadium competition and attracting global investors' attention. In her opening speech at the Taiwan Pavilion, Deputy Director-General of the Industrial Development Bureau, Ministry of Economic Affairs, Pei-Li Chen emphasized the future trend of integrating cross-disciplinary technologies for industrial development. She highlighted Taiwan's strengths in information and communication technology, comprehensive manufacturing supply chain, and excellent clinical medical capabilities, positioning the country for collaboration with other nations to develop superior biomedical products and services. Major Institutions and Global Partnerships at US BIO Six major biomedical research institutions from Taiwan, including Academia Sinica, National Health Research Institutes (NHRI), Development Center for Biotechnology (DCB), Industrial Technology Research Institute's Biomedical Technology and Device Research Laboratories, Medical and Pharmaceutical Industry Technology and Development Center (PITDC), and the Agricultural Technology Research Institute (ATRI), showcased their technological achievements in agricultural biotechnology, pharmaceuticals, and medical devices. The Taiwan Bio-Industry Organization introduced the current state of Taiwan's biotech industry and collaboration opportunities at the Global Innovation Hub event, promoting international partnerships. During the exhibition, the Taiwan team visited the Phoenix biomedical cluster, including Mayo Clinic's Barrow Neurological Institute, Translational Genomics Research Institute (TGen), along with Rakuten Medical and Tanvex to explore opportunities for joint drug development or production collaboration. SOURCE BPIPO

A massive computational analysis of microbiome datasets has more than doubled the number of known protein families. This is the first time protein structures have been used to help characterize the vast array of microbial 'dark matter.'   Imagine researchers exploring a dark room with a flashlight, only able to clearly identify what falls within that single beam. When it comes to microbial communities, scientists have historically been unable to see beyond the beam -- worse, they didn't even know how big the room is. A new study published online October 11, 2023 in Nature highlights the vast array of functional diversity of microbes through a novel approach to better understand microbial communities by looking at protein function within them. The work was led by a team of scientists at the U.S. Department of Energy (DOE) Joint Genome Institute (JGI), a DOE Office of Science User Facility located at Lawrence Berkeley National Laboratory (Berkeley Lab), and collaborators across multiple other research centers around the world. "We've more than doubled the number of protein families known up until now, and identified many novel structure predictions," said lead author on the paper Georgios Pavlopoulos, now a research director at the Biomedical Sciences Research Center Alexander Fleming. "This was a massive analysis of 1.3 billion proteins with massively parallel computations." Guided by JGI scientists, the team embarked on a mission to unveil the mysteries concealed within the "dark" functional realm. Their focus sharpened on deciphering the intricate world of protein functional diversity: the novel protein families and novel functions in as-yet unveiled microbes. Harnessing the collective power of more than 26,000 microbiome datasets, all accessible through the publicly available Integrated Microbial Genomes & Microbiomes (IMG/M) database, they successfully crafted the Novel Metagenome Protein Families (NMPF) Catalog. "We can now analyze new datasets by comparing against these protein families, or further analyze the protein families in order to predict new functions," said Nikos Kyrpides, senior author of the study and head of the JGI's Microbiome Data Science group. Shining a Light on Functional "Dark Matter" Microbial communities living everywhere from soils and stomachs to the deep sea are capable of doing a lot of unique things when it comes to energy cycles -- turning biomass into things like ethanol or hydrogen, or solar energy into hydrogen. Microbial communities are also incredibly difficult to study. Many of the microbes within them cannot be cultivated in lab settings. Since each microbial community has its own unique makeup of microbe players and the functions they perform, artificially replicating a whole community is impossible. Metagenomic sequencing allows researchers to study the entire genetic makeup of these communities via whole genome sequencing of the samples, without being able to distinguish which gene belongs to each individual microbial species within a community. Therefore, the process hinges on referencing to existing genome sequences. Some of these proteins are what the scientists call "known knowns" -- that is, they are similar to genes with known function. Others are called "known unknowns" -- that is, they are similar to previously known genes from isolate organisms, but we still aren't sure of their function. However, if a gene in the community doesn't match any of the previously known genes from isolates, there isn't much scientists can tell about its function or its origin. As a result, these genes were typically discarded from any analysis as useless information. These represent the "unknown unknowns" because they aren't similar to anything we've already defined. "A huge percentage -- around 30-50% of the protein families that we knew so far -- still does not have any known function, but we knew the families," Kyrpides said. Yet, "almost 20 years of metagenomic data and metagenomic analysis, and still there has been no real analysis of protein families from metagenomes per se." Recently, other research teams have leveraged the power of artificial intelligence to decode the language of protein sequences and obtain hints of their possible functions. Yet these efforts were limited to the realm of already-known protein sequences. "In this endeavor, we have not only ventured into the uncharted territory of understanding the vast landscape of functional diversity, but we have also pushed the boundaries by applying AI methodologies to unravel their roles," Pavlopoulos said. "Consequently, we have amassed an extensive repository of groundbreaking insights, significantly expanding the horizons of potential functions across various categories of proteins, including those with pivotal applications in biotechnology, such as DNA editing enzymes." Leveraging Protein Families in a New Way The discovery of new protein families had started to plateau in recent years, perhaps suggesting that scientists had "captured" much of the diversity out there, even if it hadn't yet defined what it did, exactly. But what kind of diversity might those "unknown unknowns" hold? The team started with 8 billion metagenome genes from IMG (the study also references data from the JGI's Genomes from Earth's Microbiome, or GEM catalog). Then they removed any genes with even a remote similarity to previously known genes, leaving them with around 1.2 billion novel genes. They took what they were left with and clustered them into families. From there they focused on families with at least 100 members. "If you have 100 sequences, the quality of the cluster is significantly higher because it is very hard to have 100 sequences from different locations or habitats that align very well, randomly," Kyrpides explained. "Replicating that 100 times would have been almost impossible." When the team was finished with this phase, they found that the protein family diversity within this metagenomic space (the "unknown unknowns") was vastly greater than that of the reference genomes -- by at least double. "As we keep on adding more samples, we're getting more protein families," Kyrpides said. "In a few years, as we keep on sequencing more metagenomes, some of the clusters that have currently 50 members or more will grow to 100 members or more as well. So, we're saying diversity has doubled, but in reality it could be three or four or five or tenfold more out there." Digging Further into an Array of Diversity While the team didn't drill down function, they were able to further characterize these families. They divided the protein families up by environment and found only 7% of protein families were shared across all eight environmental categories. Instead, families preferred a specific environment -- whether that be soil, animal hosts, marine ecosystems, etc. "So, they must be doing something interesting or important for that habitat," Pavlopoulos explained. "That is definitely material that the scientific community now can use further. Let's say somebody is working on soil environments or the human body -- they may take some of those families and try to functionally characterize them because they are very specific to that habitat." Taxonomic analysis found that the majority of these protein families belonged to bacteria and viruses, though 6 million of the sequences evaded classification. Researchers also tried to hone in on the function of the genes via 3D modeling, and comparing structures of the unknown to those of the known -- similar structure equates to high likelihood of similar function. The team also identified protein families with completely novel structures. The computational power to perform this level of analysis hinged on access to the National Energy Research Scientific Computing Center, another user facility at Berkeley Lab. "It's also a credit to Aydin Buluç's team with Berkeley Lab's Applied Mathematics and Computational Research Division," Pavlopoulos said. "They developed parallel algorithms to perform 'all-vs-all' comparisons and graph clustering able to run in such highly parallel infrastructures." This is the first time protein structures have been used to help characterize the vast array of microbial dark matter. The study took roughly two years to complete, with only about 20,000 metagenomes sequenced at the time. Now, that number is closer to 60,000. "There is still 70-80% of known microbial diversity out there that is not yet captured genomically," Kyrpides said. "So, that diversity is definitely holding a lot of new secrets in terms of functional diversity as well." Researchers from Harvard University, Indiana University. University of Crete (Greece). Georgia Institute of Technology, Michigan State University, Lawrence Livermore National Laboratory, University of Washington, Centre for Research & Technology Hellas (Greece), Aristotle University of Thessalonica (Greece), and the University of California, Berkeley were also involved in the work. Other authors on the paper are Fotis Baltoumas, Sirui Liu, Oguz Selvitopi, Antonio Camargo Stephen Nayfach, Ariful Azad, Simon Roux, Lee Call, Natalia N. Ivanova, I Min Che, David Paez-Espino, Evangelos Karatzas, Novel Metagenome Protein Families Consortium, Ioannis Iliopoulos, Konstantinos Konstantinidis, James M. Tiedje, Jennifer Pett-Ridge, David Baker, Axel Visel, Christos A. Ouzounis, and Sergey Ovchinnikov.

Diagnosis of Plasmodium falciparum malaria using rapid diagnostic tests and treatment with artemisinin derivatives, the main component of the malaria treatments recommended by the World Health Organization (WHO), are under threat in the Horn of Africa. Scientists have detected the emergence and spread in Eritrea of parasites with both artemisinin resistance and genome modifications that prevent their detection with rapid diagnostic tests, thereby jeopardizing malaria control and elimination campaigns in the region and potentially elsewhere in Africa. Diagnosis of Plasmodium falciparum malaria using rapid diagnostic tests and treatment with artemisinin derivatives, the main component of the malaria treatments recommended by the World Health Organization (WHO), are under threat in the Horn of Africa. Scientists from the Laboratory of Parasitology and Medical Mycology at the University of Strasbourg and Strasbourg University Hospital, in collaboration with the Eritrean Ministry of Health, the Institut Pasteur, Columbia University in New York and WHO, have detected the emergence and spread in Eritrea of parasites with both artemisinin resistance and genome modifications that prevent their detection with rapid diagnostic tests, thereby jeopardizing malaria control and elimination campaigns in the region and potentially elsewhere in Africa. The research results were published on September 28, 2023 in the New England Journal of Medicine. Malaria, a disease caused by parasites of the genus Plasmodium, represents a major public health problem worldwide. Plasmodium falciparum, responsible for severe forms, is found mainly in Sub-Saharan Africa, where a child dies of malaria every two minutes. In 2021, 247 million cases and 619,000 deaths were reported, a 6.4% increase compared with 2019. Current strategies to fight malaria involve prevention, with the use of insecticide-treated bed nets; diagnosis, with the introduction of rapid diagnostic tests; and treatment, which must be effective. For more than 15 years, treatment for malaria episodes (which alternate between fever, shivering and chills, and severe sweating) caused by Plasmodium falciparum in Sub-Saharan Africa has been based on artemisinin-based combination therapies (ACTs). These highly effective treatments combine a potent, fast-acting artemisinin derivative and a partner drug with a long half-life that acts more slowly to eliminate residual parasites. Unfortunately, in 2008, the first cases of artemisinin resistance were detected in South-East Asia. Resistance was defined by delayed parasite clearance from the bloodstream of patients treated with an ACT. In recent years, Plasmodium falciparum artemisinin resistance has also been reported in two regions of Sub-Saharan Africa, in Central Africa (Rwanda) and East Africa (Uganda). In this latest study, the scientists present the results of clinical trials conducted between 2016 and 2019 in Eritrea to assess the efficacy of two ACT treatments (artesunate/amodiaquine and artemether/lumefantrine) recommended for treating uncomplicated P. falciparum malaria. The clinical trials also aimed to estimate the proportion of patients with persistent P. falciparum parasitemia on day 3, the day after the last dose of ACT. In addition, the authors sought to identify molecular signatures in the Pfkelch13 gene associated with artemisinin resistance in parasites and to detect deletions of the hrp2 and hrp3 genes which are known to render rapid diagnostic tests ineffective in detecting parasites. The data obtained revealed another hotspot of artemisinin resistance, in Eritrea. This novel area of resistance is more worrying than those observed in Rwanda and Uganda as the investigations reveal the emergence and spread of a new artemisinin-resistant variant, Pfkelch13 622I, accompanied by hrp2 and hrp3 gene deletions in around 17% of cases, making it impossible to detect these parasite strains using rapid tests. According to the published data, it seems that the phenomenon is not recent and that these strains have been circulating in western Eritrea for several years. The findings therefore show how P. falciparum is capable of evading strategies introduced to control and eliminate malaria. "These data are a real cause for concern and undermine the quality of the health management of malaria patients in the region," warns Dr. Selam Mihreteab, a contributor to the study in Eritrea at the National Malaria Control Program, Ministry of Health. "We need to develop constant surveillance of the evolution of these parasites and their ability to spread," adds Dr. Lucien Platon, a PhD student at the Institut Pasteur (Malaria Parasite Biology and Vaccines Unit). "The strategies implemented in the Horn of Africa are under threat, not only because artemisinin resistant parasites are not detected by rapid tests but also because of the ability of malaria vectors to resist insecticides and because we have recently seen the arrival of a new mosquito species, Anopheles stephensi, capable of transmitting these strains in urban environments. There is a risk that these biological threats could lead to a rapid spread of these parasites in the region and beyond," analyzes Professor Didier Ménard, Director of the Institute of Parasitology and Tropical Diseases at the University of Strasbourg and a scientist in the Malaria Parasite Biology and Vaccines Unit at the Institut Pasteur. Over the past two decades, the proactive strategy pursued by the Eritrean government has led to a significant reduction in malaria-related morbidity and mortality in the country. These new data seem to confirm that monitoring the emergence and spread of drug resistance must be a priority in areas such as Eritrea, where strategies to reduce malaria transmission are being effectively implemented, and that there is an urgent need to develop and introduce innovative control strategies. This research received support from the Bill and Melinda Gates Foundation (WHO), the Global Fund (Ministry of Health in Eritrea), the Institut Pasteur, the French Government (National Research Agency), the University of Strasbourg (IdEX Program), and the United States Department of Defense and National Institutes of Health.