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Cell Biology

Dren Bio Announces $65 Million Series B Financing to Advance its Lead Asset into the Clinic and to Accelerate Development of New Product Candidates…

FOSTER CITY, Calif.--(BUSINESS WIRE)--Dren Bio, Inc. (Dren Bio or the Company) today announced the completion of their $65 million Series B financing, pushing the Companys total capital received to date over $156 million. Following the financing, Dren Bio is well-capitalized to reach multiple key inflection points across both its drug discovery programs over the coming years.

We are truly grateful for all the support we continue to receive from such an outstanding syndicate of investors, said Nenad Tomasevic, Ph.D., Chief Executive Officer of Dren Bio. This financing comes at the perfect time as we prepare to initiate the first clinical trial evaluating DR-01, our lead asset, in patients with Large Granular Lymphocytic leukemia or cytotoxic lymphomas in mid-2022. In addition to advancing DR-01, the proceeds from this latest round will also enable us to further expand the development of our internal pipeline using our proprietary Targeted Myeloid Engager and Phagocytosis Platform.

The Series B financing was co-led by Aisling Capital and HBM Healthcare Investments, with participation by new marquee investors Pfizer, ArrowMark Partners and Revelation Partners. There was also significant participation in the round by Dren Bios existing insiders SR One, 8VC, Taiho Ventures, BVF Partners, Mission BioCapital and Alexandria Venture Investments, amongst others. In connection with the closing of the financing, the Company announced that Andrew Schiff, M.D., of Aisling Capital, and Chandra P. Leo, M.D., of HBM Partners, will join its Board of Directors.

We were thoroughly impressed by Dren Bios diversified R&D portfolio that encompasses two distinct therapeutic antibody programs including their attractive proprietary platform, said Dr. Schiff, Managing Partner at Aisling Capital. We are excited by the opportunity to support Dren Bio in progressing on their mission to deliver revolutionary therapies to patients with severe unmet needs, starting with difficult-to-treat cancers.

Dr. Leo, of HBM Partners, added, Over the last 18 months, Dren Bio has delivered robust preclinical data for their lead asset DR-01 and for their unique technology to induce myeloid cell engagement and phagocytosis. With this new financing, the Company is well positioned to rapidly advance DR-01 towards clinical proof-of-concept and to demonstrate the broad potential of their highly differentiated platform.

Proceeds from the financing will enable Dren Bio to continue advancement of its broad internal pipeline comprised of multiple development candidates approaching the clinic. The Companys lead asset, DR-01, is designed to precisely eliminate a subset of immune cells which are the underlying cause of certain hematologic malignancies and well-defined autoimmune disorders, both of which will be evaluated using its current funding. Dren Bios position as an emerging leader in the antibody therapeutics space is further strengthened by the exceptional prospects of its Targeted Myeloid Engager and Phagocytosis Platform. Bispecific antibodies generated using the proprietary platform have been shown to produce effects that are well-differentiated from other competing technologies including T cell engagers, antibody-dependent cellular cytotoxicity (ADCC) antibodies and antibody-drug conjugates. In addition to their profound and multi-pronged mechanism of action, initial development candidates have been very well tolerated in non-human primates, which should enable their utilization in both oncology and non-oncology indications. With its current funding, Dren Bio now has the opportunity to demonstrate the vast potential of its platform to produce therapies for a wide array of patients.

About Dren Bio

Dren Bio is a privately held, clinical-stage biopharmaceutical company focused on developing therapeutic antibodies for the treatment of cancer, autoimmune and other serious diseases. The Companys senior leadership team and scientific advisors have significant expertise covering the discovery and development of antibody-based product candidates designed to selectively target and deplete pathologic cells, protein aggregates and other disease-causing agents. Dren Bios pipeline encompasses two distinct programs, the first focusing on the engineering of antibodies with enhanced antibody-dependent cellular cytotoxicity (ADCC) capabilities and the second revolving around its proprietary Targeted Myeloid Engager and Phagocytosis Platform. For more information about Dren Bio and its two programs, please visit the Companys website at http://www.drenbio.com.

About Dren Bios Enhanced ADCC Program

Dren Bios Enhanced ADCC Program incorporates a validated and well understood technology for which the Companys senior leadership team has extensive experience. The lead product candidate from this program, DR-01, has been shown preclinically to induce rapid ADCC of a cell type that possesses intrinsic cytotoxic potential and is the primary driver of disease in several rare, hematologic malignancies. In addition to these initial cancers, DR-01 is also being evaluated for potential use in treating a number of other indications, including various autoimmune disorders for which the same cytotoxic immune cells are known to play a key role.

About Dren Bios Targeted Myeloid Engager and Phagocytosis Platform

The Companys Targeted Myeloid Engager and Phagocytosis Platform is an innovative and scientifically compelling approach towards discovering bispecific antibodies for the co-engagement of a conserved, microbial phagocytic receptor highly expressed on myeloid cells, along with a specific target antigen expressed on a pathologic cell or other disease-causing agent of interest. The unique biology of the novel phagocytic receptor enables controlled myeloid cell activation only in the presence of the desired target antigen, thereby resulting in localized cytokine release for an increased therapeutic index and more favorable safety profile. Bispecific antibodies from the platform that are being developed for the treatment of cancer elicit a powerful, multi-pronged mechanism of action that encompasses (i) direct coupling of myeloid cells with cancer cells, (ii) stimulation of myeloid cells for the release of key cytokines known to reprogram tumor associated macrophages and reset the immunosuppressive tumor microenvironment, (iii) phagocytosis and killing of tumor cells, and (iv) presentation of tumor neoantigens for activating effector and memory T cell responses necessary to achieve anti-tumor immunity. The significant upregulation of Antigen Presenting Machinery (APM) signature genes and boost to both the number and diversity of peptides presented, collectively support the potential of future drug candidates discovered using the platform to provide longer-lasting responses than those currently observed by other comparable immune cell engaging technologies.

Dren Bios first development candidate using the platform, DR-0201, co-engages a validated target expressed on the surface of B cells. Exciting preclinical data generated to date from both functional assays and in vivo animal models consistently demonstrate the ability of DR-0201 to induce robust B cell depletion using a differentiated approach when compared head-to-head against ADCC antibody and T cell engager technologies. DR-0201 also consistently exhibits an attractive safety profile, which has now been observed in multiple studies of non-human primates. In addition to Dren Bios initial efforts focused on difficult-to-treat cancers, DR-0201 is being evaluated in autoimmune disorders for which the depletion of B cells has previously been validated in patients. Beyond DR-0201, the Companys early-stage pipeline also includes the discovery of bispecific antibodies against well-known solid tumor targets as well as exciting new development opportunities to potentially treat severe, life-threatening non-oncology indications such as light chain (AL) amyloidosis, transthyretin (ATTR) amyloidosis, and Alzheimers disease, through the removal of harmful protein aggregates.

Source: Dren Bio, Inc.

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Dren Bio Announces $65 Million Series B Financing to Advance its Lead Asset into the Clinic and to Accelerate Development of New Product Candidates...

Cell Biology

New Comprehensive Map Ties Every Human Gene to Its Function – SciTechDaily

Data for a new gene-function map are available for other scientists to use. Its a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research, says Professor Jonathan Weissman.

Scientists used their single-cell sequencing tool Perturb-seq on every expressed gene in the human genome, linking each to its job in the cell.

Genetics research has advanced rapidly over the last few decades. For example, just a few months ago scientists announced the first complete, gap-free human genome sequencing. Now researchers have advanced again, creating the first comprehensive functional map of genes that are expressed in human cells.

The Human Genome Project was an ambitious initiative to sequence every piece of human DNA. The project drew together collaborators from research institutions around the world, including MITs Whitehead Institute for Biomedical Research, and was finally completed in 2003. Now, over two decades later, MIT Professor Jonathan Weissman and colleagues have gone beyond the sequence to present the first comprehensive functional map of genes that are expressed in human cells. The data from this project, published online on June 9, 2022, in the journal Cell, ties each gene to its job in the cell, and is the culmination of years of collaboration on the single-cell sequencing method Perturb-seq.

The data are available for other scientists to use. Its a big resource in the way the human genome is a big resource, in that you can go in and do discovery-based research, says Weissman, who is also a member of the Whitehead Institute and an investigator with the Howard Hughes Medical Institute. Rather than defining ahead of time what biology youre going to be looking at, you have this map of the genotype-phenotype relationships and you can go in and screen the database without having to do any experiments.

CRISPR, which stands for clustered regularly-interspaced short palindromic repeats, a genome editing tool invented in 2009 made it easier than ever to edit DNA. It is easier, faster, less expensive, and more accurate than previous genetic editing methods.

The screen allowed the researchers to delve into diverse biological questions. They used it to explore the cellular effects of genes with unknown functions, to investigate the response of mitochondria to stress, and to screen for genes that cause chromosomes to be lost or gained, a phenotype that has proved difficult to study in the past. I think this dataset is going to enable all sorts of analyses that we havent even thought up yet by people who come from other parts of biology, and suddenly they just have this available to draw on, says former Weissman Lab postdoc Tom Norman, a co-senior author of the paper.

Pioneering Perturb-seq

The project takes advantage of the Perturb-seq approach that makes it possible to follow the impact of turning on or off genes with unprecedented depth. This method was first published in 2016 by a group of researchers including Weissman and fellow MIT professor Aviv Regev, but could only be used on small sets of genes and at great expense.

The massive Perturb-seq map was made possible by foundational work from Joseph Replogle, an MD-PhD student in Weissmans lab and co-first author of the present paper. Replogle, in collaboration with Norman, who now leads a lab at Memorial Sloan Kettering Cancer Center; Britt Adamson, an assistant professor in the Department of Molecular Biology at Princeton University; and a group at 10x Genomics, set out to create a new version of Perturb-seq that could be scaled up. The researchers published a proof-of-concept paper in Nature Biotechnology in 2020.

The Perturb-seq method uses CRISPR-Cas9 genome editing to introduce genetic changes into cells, and then uses single-cell RNA sequencing to capture information about the RNAs that are expressed resulting from a given genetic change. Because RNAs control all aspects of how cells behave, this method can help decode the many cellular effects of genetic changes.

Since their initial proof-of-concept paper, Weissman, Regev, and others have used this sequencing method on smaller scales. For example, the researchers used Perturb-seq in 2021 to explore how human and viral genes interact over the course of an infection with HCMV, a common herpesvirus.

In the new study, Replogle and collaborators including Reuben Saunders, a graduate student in Weissmans lab and co-first author of the paper, scaled up the method to the entire genome. Using human blood cancer cell lines as well noncancerous cells derived from the retina, he performed Perturb-seq across more than 2.5 million cells, and used the data to build a comprehensive map tying genotypes to phenotypes.

Delving into the data

Upon completing the screen, the researchers decided to put their new dataset to use and examine a few biological questions. The advantage of Perturb-seq is it lets you get a big dataset in an unbiased way, says Tom Norman. No one knows entirely what the limits are of what you can get out of that kind of dataset. Now, the question is, what do you actually do with it?

The first, most obvious application was to look into genes with unknown functions. Because the screen also read out phenotypes of many known genes, the researchers could use the data to compare unknown genes to known ones and look for similar transcriptional outcomes, which could suggest the gene products worked together as part of a larger complex.

The mutation of one gene called C7orf26 in particular stood out. Researchers noticed that genes whose removal led to a similar phenotype were part of a protein complex called Integrator that played a role in creating small nuclear RNAs. The Integrator complex is made up of many smaller subunits previous studies had suggested 14 individual proteins and the researchers were able to confirm that C7orf26 made up a 15th component of the complex.

They also discovered that the 15 subunits worked together in smaller modules to perform specific functions within the Integrator complex. Absent this thousand-foot-high view of the situation, it was not so clear that these different modules were so functionally distinct, says Saunders.

Another perk of Perturb-seq is that because the assay focuses on single cells, the researchers could use the data to look at more complex phenotypes that become muddied when they are studied together with data from other cells. We often take all the cells where gene X is knocked down and average them together to look at how they changed, Weissman says. But sometimes when you knock down a gene, different cells that are losing that same gene behave differently, and that behavior may be missed by the average.

The researchers found that a subset of genes whose removal led to different outcomes from cell to cell were responsible for chromosome segregation. Their removal was causing cells to lose a chromosome or pick up an extra one, a condition known as aneuploidy. You couldnt predict what the transcriptional response to losing this gene was because it depended on the secondary effect of what chromosome you gained or lost, Weissman says. We realized we could then turn this around and create this composite phenotype looking for signatures of chromosomes being gained and lost. In this way, weve done the first genome-wide screen for factors that are required for the correct segregation of DNA.

I think the aneuploidy study is the most interesting application of this data so far, Norman says. It captures a phenotype that you can only get using a single-cell readout. You cant go after it any other way.

The researchers also used their dataset to study how mitochondria responded to stress. Mitochondria, which evolved from free-living bacteria, carry 13 genes in their genomes. Within the nuclear DNA, around 1,000 genes are somehow related to mitochondrial function. People have been interested for a long time in how nuclear and mitochondrial DNA are coordinated and regulated in different cellular conditions, especially when a cell is stressed, Replogle says.

The researchers found that when they perturbed different mitochondria-related genes, the nuclear genome responded similarly to many different genetic changes. However, the mitochondrial genome responses were much more variable.

Theres still an open question of why mitochondria still have their own DNA, said Replogle. A big-picture takeaway from our work is that one benefit of having a separate mitochondrial genome might be having localized or very specific genetic regulation in response to different stressors.

If you have one mitochondria thats broken, and another one that is broken in a different way, those mitochondria could be responding differentially, Weissman says.

In the future, the researchers hope to use Perturb-seq on different types of cells besides the cancer cell line they started in. They also hope to continue to explore their map of gene functions, and hope others will do the same. This really is the culmination of many years of work by the authors and other collaborators, and Im really pleased to see it continue to succeed and expand, says Norman.

Reference: Mapping information-rich genotype-phenotype landscapes with genome-scale Perturb-seq by Joseph M. Replogle, Reuben A. Saunders, Angela N. Pogson, Jeffrey A. Hussmann, Alexander Lenail, Alina Guna, Lauren Mascibroda, Eric J. Wagner, Karen Adelman, Gila Lithwick-Yanai, Nika Iremadze, Florian Oberstrass, Doron Lipson, Jessica L. Bonnar, Marco Jost, Thomas M. Norman and Jonathan S. Weissman, 9 June 2022, Cell.DOI: 10.1016/j.cell.2022.05.013

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New Comprehensive Map Ties Every Human Gene to Its Function - SciTechDaily

Cell Biology

SG$25 million grant awarded to multi-institution research team working to improve liver cancer outcomes – EurekAlert

Singapore, 13 June 2022 A multidisciplinary team of clinician-scientists and researchers has been awarded a SG$25 million grant to conduct clinical and translational studies and cutting-edge patient-data analysis that will lead to improvements in clinical practice and better health outcomes for patients with the primary liver cancer, hepatocellular carcinoma (HCC). Led by the National Cancer Centre Singapore (NCCS) in collaboration with A*STARs Genome Institute of Singapore (GIS) and Institute of Molecular and Cell Biology (IMCB), the Cancer Science Institute of Singapore, at the National University of Singapore, and Duke-NUS Medical School, the PLANet 2.0 (Precision Medicine in Liver Cancer across an Asia-Pacific Network) research programme is supported by the National Research Foundation Singapore under its Open Fund-Large Collaborative Grant (OFLCG21Jun-0016) which is administered by the Singapore Ministry of Healths National Medical Research Council (NMRC).

Liver cancer is the sixth most common cancer in the world and fourth most common cause of cancer deaths globally.[1] In Singapore, it is the third most common cause of cancer deaths in males and fifth most common cause in females[2]; as HCC is usually diagnosed at a late stage, when prognosis is poor. In addition, current standard therapies for HCC, including systemic therapies, have poorer efficacy compared to systemic treatment for other common cancers. This is largely because there are currently no validated biomarkers to guide clinicians in the choice of the best therapy for an individual patient with HCC.

PLANet 2.0 builds on the success of our earlier programme, PLANet 1.0, bringing together leading clinical and translational research experts across Singapore to address the urgent, unmet clinical need for more targeted and efficient treatment for liver cancer so that patients may have better outcomes, said Professor Pierce Chow, Principal Investigator of the study and Senior Consultant, Department of Hepato-Pancreato-Biliary and Transplant Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital and NCCS.

Laying the foundation for PLANet 2.0

The PLANet 2.0 research team first came together in 2016 for PLANet 1.0, a five-year multidisciplinary research programme to better understand the tumour biology and mechanisms of HCC. Detailed understanding of the landscape of HCC and robust predictive biomarkers is key to improving clinical outcomes in HCC. Current clinical practice and treatment recommendations for HCC are hindered by the absence of biomarkers that can guide therapy and therefore depend on the individual clinicians judgement, experience and preference.

While immunotherapy is currently the most effective systemic therapy for HCC, only a subset of patients responds to it, with 30% being the best overall response rate. PLANet 1.0 found that HCCs molecular landscape is extremely heterogeneous and shed light on novel mechanisms underpinning the disease, including how it reverts to foetal forms to escape the bodys immunological defence, highlighting why HCC is difficult to treat.[3]

Conducting PLANet 2.0 in Singapore and the region

PLANet 2.0 will conduct two clinical studies that will serve as proof-of-concept for PLANet 1.0s translational findings and allow the team to uncover predictive biomarkers. In the first clinical study, a minimum of 30 patients with HCC who have undergone liver resection or surgery for the tumour will receive immunotherapy after surgery to reduce the chance of the tumour coming back. The second clinical study is a randomised controlled trial for patients with intermediate to advanced HCC ineligible for surgery. These surgically unresectable patients will be treated with Selective Internal Radiation Therapy (SIRT) with yttrium-90 followed by immunotherapy in a novel radiotherapy and immunotherapy combination. This study will enrol 176 patients. The two clinical studies will run concurrently and the recruitment and administration of the clinical studies will be in multiple sites in Singapore (Changi General Hospital, National Cancer Centre Singapore, National University Cancer Institute, Singapore, National University Hospital, Sengkang General Hospital, Singapore General Hospital and Tan Tock Seng Hospital) and 11 other hospitals in the Asia-Pacific region.

These studies leverage their longitudinal study designs to obtain before and after treatment patient samples and clinical data and aim to identify and validate biomarkers that correlate with clinical outcomes including response and resistance to therapy. The research teams will use a wide spectrum of investigations leveraging on their multidisciplinary expertise in the fields of epigenomics, genomics, immunomics, metabolomics, proteomics, data science and clinical care to better understand the landscape of the HCC tumour micro-environment and biomarker co-localisation. This convergence of approaches will enable robust validation of conclusions and inform the change needed in clinical practice to institute more efficacious and personalised treatment for HCC patients in the future.

Dr Tam Wai Leong, Associate Director and Group Leader of the Laboratory of Translational Cancer Biology at GIS, as well as Theme PI, said, GIS is excited to be part of this multi-disciplinary and multi-institutional study aimed at improving clinical outcomes for liver cancer patients. The project will harness the power of genomic technologies to unlock the secrets of disease genes through deep profiling of consented clinical trial biosamples. The longitudinal tracking of tumours from the same patients will reveal critical genetic insights on why some cancer patients fare better than others, ultimately aiding in tailoring better treatment strategies for patients.

Professor Vinay Tergaonkar, Research Director at IMCB and Theme PI, said, Although the composition of various types of cells that constitute a tumour are well-studied in many cancers including HCC, this study would be one of the first ever, wherein changes in the physical co-localisation of various cell populations of the HCC microenvironment will be deciphered during the course of therapy. This information will be beneficial in guiding future therapeutic development.

The Open Fund-Large Collaborative Grant (OF-LCG) Programme

The annual OF-LCG grant call supports the efforts of the best research teams in Singapore to conduct patient-centric translationalresearch with the goal of advancing human health and wellness and creating economic value. Cancer is one of the seven areas identified as national priorities for research in Singapore.

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About the National Cancer Centre of Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. NCCS attends to the majority of cancer cases in Singapores public healthcare sector. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve the vision of being a global leading cancer centre, NCCS offers world class care and shares its depth of experience and expertise by training local and overseas medical professionals.

To meet growing needs, the new NCCS building will be completed in 2022 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, NCCS will offer access to advanced and innovative treatment such as proton therapy at the new Goh Cheng Liang Proton Therapy Centre.

For more information, please visit: http://www.nccs.com.sg

About the Agency for Science, Technology and Research (A*STAR)

A*STAR is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STARs R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit http://www.a-star.edu.sg.

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About A*STARs Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS pursues the integration of technology, genetics and biology towards academic, economic and societal impact, with a mission to "read, reveal and write DNA for a better Singapore and world".

Key research areas at the GIS include Precision Medicine & Population Genomics, Genome Informatics, Spatial & Single Cell Systems, Epigenetic & Epitranscriptomic Regulation, Genome Architecture & Design, and Sequencing Platforms. The genomics infrastructure at the GIS is also utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit http://www.a-star.edu.sg/gis.

About A*STARs Institute of Molecular and Cell Biology (IMCB)

The vision of Institute of Molecular and Cell Biology (IMCB) is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with the public sector, medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapores transformation into an international hub for biomedical research, development and innovation.

Funded by A*STAR, IMCBs use-inspired research comprises 4 major programmes: Neurometabolism in Health and Diseases; Cancer Signalling and Therapies; Cell Biology and Therapies; and Innovative Technologies IMCBs technologies and platforms focus on Mouse Models of Diseases, Molecular Histopathology, Cellular Microscopy, and Proteomics & Metabolomics. For more information about IMCB, please visit http://www.a-star.edu.sg/imcb.

About the Cancer Science Institute of Singapore (CSI Singapore)

The Cancer Science Institute of Singapore (CSI) is one of only six Research Centres of Excellence established by the Government of Singapore with funding from the National Research Foundation and the Ministry of Education. Its mission is to better understand the causes of human cancer across Asia, and thereby improve its detection, treatment and prevention for the benefit of the patients. The CSIs outstanding researchers and excellent scientific facilities create an energetic environment for ground-breaking research and world-class training. The CSI is internationally recognized for its innovative research on the biology of cancers prevalent in Asia, and for taking new methods for cancer treatment from the laboratory to the clinic. Through its local and global partnerships,the CSI works with leading minds from multiple scientific and clinical disciplines in Singapore, the USA and Europe, both in academia and in industry. For more information on CSI Singapore, visit https://www.csi.nus.edu.sg/web/

About Duke-NUS Medical School

Duke-NUS is Singapores flagship graduate entry medical school, established in 2005 with a strategic, government-led partnership between two world-class institutions: Duke University School of Medicine and the National University of Singapore (NUS). Through an innovative curriculum, students at Duke-NUS are nurtured to become multi-faceted Clinicians Plus poised to steer the healthcare and biomedical ecosystem in Singapore and beyond. A leader in ground-breaking research and translational innovation, Duke-NUS has gained international renown through its five signature research programmes and 10 centres. The enduring impact of its discoveries is amplified by its successful Academic Medicine partnership with Singapore Health Services (SingHealth), Singapores largest healthcare group. This strategic alliance has spawned 15 Academic Clinical Programmes, which harness multi-disciplinary research and education to transform medicine and improve lives.

For more information, please visit http://www.duke-nus.edu.sg

For more information, please contact:

National Cancer Centre Singapore

Dharshini Subbiah

Assistant Manager, Corporate Communications

Mobile : 9616 7532

Email : dharshini.subbiah@nccs.com.sg

Agency for Science, Technology and Research (A*STAR)

Sharmaine Loh

Assistant Head, Corporate Communications

Mobile: 98621834

Email: sharmaine_loh@hq.a-star.edu.sg

[1] Singal, A. G., Lampertico, P. & Nahon, P. Epidemiology and surveillance for hepatocellular carcinoma: New trends. J. Hepatol. 72, 250261 (2020)

[2] National Registry of Diseases Office. (2022, Jan).Singapore Cancer Registry Annual Report 2019.

[3] Zhai, W. et al. Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in Hepatocellular Carcinoma: the PLANET study. Natl. Sci. Rev. (2021) doi:10.1093/nsr/nwab192

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SG$25 million grant awarded to multi-institution research team working to improve liver cancer outcomes - EurekAlert

Cell Biology

Postdoctoral Researcher / Doctoral Researcher in the Functional Cancer Genomics Group job with UNIVERSITY OF HELSINKI | 297116 – Times Higher…

The Functional Cancer Genomics group led by Dr. Sakari Vanharanta at the Translational Cancer Medicine Program, Faculty of Medicine, University of Helsinki, Finland, invites applications for the position of

POSTDOCTORAL RESEARCHER / DOCTORAL RESEARCHER

The goal of our research is to understand how cancers develop and spread, and how this knowledge could be used for the development of new approaches for therapy. We study how cancer mutations activate oncogenic programs and how these programs lead to cancer progression and metastasis. Specifically, our aims are to understand (i) how normal transcriptional programs are co-opted for carcinogenesis, (ii) how these programs interact with genetically activated oncogenic pathways, (iii) what the critical pro-tumorigenic mechanisms of cancer mutations are, and (iv) whether cancer-specific cellular programs lead to molecular vulnerabilities that could be exploited for cancer therapy and patient benefit. Our research combines experimental cancer models and human cancer data sets with state-of-the-art genomics (e.g. chromatin and transcriptional profiling), mechanistic analysis using various methods of genetic perturbation, and unbiased functional genetic screens (e.g. CRISPR/Cas9 screens), as demonstrated by our recent work (Patel et al. Nature 2022).

The Functional Cancer Genomics group consists of biomedical scientists with diverse backgrounds and expertise. We have strong international connections and work in a collaborative manner towards shared goals. After eight years at the University of Cambridge, the team has recently moved to Helsinki, and is located at Biomedicum Helsinki within the Academic Medical Center Helsinki, which provides a multidisciplinary research environment for basic and translational research with state-of-the-art facilities, cutting-edge technologies and synergistic expertise of several research groups.

We are looking for highly motivated biomedical scientists with a strong background in molecular and cell biology, biochemistry, functional genomics, cancer biology, genetics, computational biology, bioinformatics, or other related disciplines. At the postdoctoral level a successful candidate should have a PhD degree in an appropriate biological subject and a demonstrated track record of peer-reviewed publications. At the pre-doctoral level, previous experience in biomedical research or bioinformatics is considered an advantage.

Candidates should be able to demonstrate abstract thinking as well as potential to develop and pursue scientific projects in the field of cancer biology. Excellent communication skills in English and organizational abilities are expected. The position is available as soon as the selected candidates are available. The project allows initially a three-year fixed-term position. Salary will be commensurate with qualifications and experience based on the University guidelines.

Please submit your application as a single PDF file through the Universitys electronic recruitment system. If you need technical support with the recruitment system, please contact recruitment@helsinki.fi.

The deadline for applications is 25 July 2022.

Please attach the following documents to your application as a single PDF file:

For more information on the positions and specific projects, please contact Dr. Sakari Vanharanta, sakari.vanharanta@helsinki.fi.

More information on the Translational Cancer Medicine Program can be found here.

For additional information about the application process, please contact the HR team at hr-ltdk@helsinki.fi.

Relevant publications:

Patel et al. The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer. Nature (2022). https://doi.org/10.1038/s41586-022-04809-8Patel et al. Genomic control of metastasis. Br J Cancer. (2021) Jan;124(1):3-12.Rodrigues et al. NF-kappaB-dependent lymphoid enhancer co-option promotes renal carcinoma metastasis. Cancer Discov. (2018), Jul;8(7):850-865

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Postdoctoral Researcher / Doctoral Researcher in the Functional Cancer Genomics Group job with UNIVERSITY OF HELSINKI | 297116 - Times Higher...

Cell Biology

OSU researchers study quorum sensing in a gram-negative bacterium that displays social behaviors – News-Medical.Net

Oregon State University scientists have identified proteins that prevent a bacterial cell from becoming misguided by its own messaging, allowing it to instead wait for collective communication from its group.

The research is important because understanding this type of signaling, known as quorum sensing and integral to bacterial pathogens, opens the door to potential new drugs that can disrupt it and thwart infection.

Findings were published today in the Proceedings of the National Academy of Sciences.

Martin Schuster, a professor in OSU's Department of Microbiology in the colleges of Science and Agricultural Sciences, and doctoral student Parker Smith study quorum sensing in the pathogen Pseudomonas aeruginosa, a gram-negative bacterium that displays a variety of social behaviors.

P. aeruginosa, a common cause of lung and wound infections among hospital patients and people with weakened immune systems, is a model organism for quorum sensing research with a well understood signaling circuit, the scientists said.

"Sometimes single-celled organisms need to work together with other cells," Schuster said. "Bacteria and other single-celled microbes can coordinate behaviors and act as a group via quorum sensing, in which cells produce and sense a small chemical signal that is shared within the population."

As the signal is released from cells and reaches a high enough concentration in their environment, a quorum is achieved certain genes are simultaneously activated and specific group behaviors are set in motion, Smith said.

It's a strength-in-numbers approach that allows bacteria to join forces to do things they could not do by themselves, like causing infection in animals and plants, acquiring certain nutrients and competing against other microbes.

"Bacterial infection often involves toxins that only harm the host at high levels, when produced by all bacterial cells at once," Smith said.

A major unresolved question about quorum sensing, the researchers said, has been why the signal that's produced inside an individual cell is not sensed by that same cell before it is released, spurring the cell into premature, solo action.

"In essence, what prevents signal 'short-circuiting' from happening?" Schuster said. "Our research addresses this question that's fundamental to our understanding of quorum sensing."

Smith and Schuster learned that a set of proteins called antiactivators are crucial for short-circuit prevention. The proteins work as a quorum sensing "tuner" by causing cells to be less sensitive to the quorum signal.

The researchers developed bacterial strains that lacked two different types of antiactivator proteins and then looked at quorum sensing behaviors in individual cells.

"We found that without antiactivators, a fraction of cells in a P. aeruginosa population engaged in 'self-talk,'" Smith said. "In these cells, signal short-circuiting had activated quorum-sensing-dependent behaviors at all times, irrespective of cell density and without any communication with other cells. Our research shows how bacteria put the brakes on quorum sensing to achieve true communication in a group."

In addition to helping the quest for new antibiotics that can inhibit quorum sensing in bacterial pathogens, the findings also provide background knowledge useful for the engineering of cells with new properties in a field called synthetic biology, Schuster said.

The study was funded by the National Science Foundation.

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Cell Biology

3D Cell Culture Market by Type, Application, End-user and Region – Global Forecast to 2027 – GlobeNewswire

Dublin, June 08, 2022 (GLOBE NEWSWIRE) -- The "3D Cell Culture Market by Type (Hydrogel, ECM, Hanging Drop, Bioreactor, Microfluidics, Magnetic Levitation), Application (Cancer, Stem Cell, Toxicology, Tissue Engineering), End User (Pharma, Biotech, Research, Cosmetics), Region - Global Forecast to 2027" report has been added to ResearchAndMarkets.com's offering.

The global 3D cell culture market is valued at an estimated USD 1.3 billion in 2022 and is projected to reach USD 2.6 billion by 2027, at a CAGR of 15.6% during the forecast period.

The growth of this market is mainly driven by factors such as the increasing focus on developing alternative methods to animal testing, growing focus on personalized medicine, increasing incidence of chronic diseases, and the availability of funding for research. On the other hand, a lack of infrastructure for 3D cell-based research and the high cost of cell biology research are expected to restrain the growth of this market during the forecast period.

The scaffold-based 3D cell culture segment accounted for the highest growth rate in the 3D Cell culture market, by type, during the forecast period

In 2021, the scaffold-based 3D cell culture segment accounted for the highest growth rate. The advantages of scaffolds in 3D cell culture, such as structural rigidity, the availability of attachment points, and support, have greatly driven the preference for scaffold-based 3D cell cultures and ensured the large share of this segment.

Asia Pacific: The fastest-growing region in the 3D Cell culture market

The Asia Pacific market is estimated to record the highest CAGR during the forecast period. This is attributed to the presence of favorable regulatory guidelines, government support for cell culture-based vaccine production, low manufacturing costs, and the growing focus of global market players on emerging Asian countries.

Key Topics Covered:

1 Introduction

2 Research Methodology

3 Executive Summary

4 Premium Insights4.1 3D Cell Culture Market Overview4.2 North America: 3D Cell Culture Market, by Type and Country (2021)4.3 3D Cell Culture Market Share, by Application, 2022 Vs. 20274.4 3D Cell Culture Market Share, by End-user, 2021 (USD Million)4.5 3D Cell Culture Market: Geographic Growth Opportunities

5 Market Overview5.1 Introduction5.2 Market Dynamics5.2.1 Drivers5.2.1.1 Increasing Focus on Developing Alternatives to Animal Testing5.2.1.2 Growing Focus on Personalized Medicine5.2.1.3 Increasing Incidence of Chronic Diseases5.2.1.4 Availability of Funding for Research5.2.1.5 Growing Demand for 3D Cell Culture5.2.2 Restraints5.2.2.1 Lack of Infrastructure for 3D Cell-Based Research5.2.2.2 High Cost of Cell Biology Research5.2.3 Opportunities5.2.3.1 Emergence of Microfluidics-Based 3D Cell Culture5.2.3.2 Emerging Economies5.2.3.3 Regenerative Medicine as An Alternative to Organ Transplantation5.2.3.4 Risk of Pandemics and Communicable Diseases5.2.4 Challenges5.2.4.1 Lack of Consistency in 3D Cell Culture Products5.2.4.2 Plastic Waste Disposal5.3 Ranges/Scenarios5.4 Impact of the COVID-19 Outbreak on the 3D Cell Culture Market5.5 Pricing Analysis5.6 Technology Analysis5.7 Patent Analysis5.8 Value Chain Analysis5.9 Supply Chain Analysis5.10 Ecosystem Analysis of the 3D Cell Culture Market5.11 Key Conferences & Events in 2022-20235.12 Regulatory Analysis5.12.1 Regulatory Bodies, Government Agencies, and Other Organizations5.13 Porter's Five Forces Analysis5.14 Key Stakeholders and Buying Criteria

6 3D Cell Culture Market, by Type6.1 Introduction6.2 Scaffold-Based 3D Cell Cultures6.2.1 Hydrogels/Ecm Analogs6.2.1.1 Hydrogels/Ecm Analogs Dominate the Scaffold-Based 3D Cell Cultures Market6.2.2 Solid Scaffolds6.2.2.1 Solid Scaffolds Are Widely Adopted in Regenerative Medicine and Preclinical in Vitro Testing6.2.3 Micropatterned Surfaces6.2.3.1 Micropatterned Surfaces Enhance the Expression of Enzymes Levels and Drug Reactivity6.3 Scaffold-Free 3D Cell Cultures6.3.1 Low Attachment Plates6.3.1.1 Low Attachment Plates Are Expected to Grow at the Highest Rate in the Scaffold-Free 3D Cell Cultures Market6.3.2 Hanging Drop Plates6.3.2.1 Hanging Drop Plates Are Widely Used in Stem Cell Differentiation and Cytotoxicity Research6.3.3 3D Bioreactors6.3.3.1 3D Bioreactors Are Commonly Used in the Mass Production of Cells6.3.4 3D Petri Dishes6.3.4.1 Europe Will Witness the Highest Growth in the 3D Petri Dishes Market6.4 Microfluidics-Based 3D Cell Cultures6.4.1 Microfluidics-Based 3D Cell Cultures Will Grow at the Highest Rate in the 3D Cell Culture Market6.5 Magnetic & Bioprinted 3D Cell Cultures6.5.1 3D Cell Culture Can be Formed Without Media in Magnetic Levitation

7 3D Cell Culture Market, by Application7.1 Introduction7.2 Cancer & Stem Cell Research7.2.1 Rising Prevalence of Cancer is a Key Factor Driving the Growth of this Segment7.3 Drug Discovery & Toxicology Testing7.3.1 Increasing Adoption of Personalized Medicines to Support Market Growth7.4 Tissue Engineering & Regenerative Medicine7.4.1 Increasing Tissue Engineering & Regenerative Medicine Research to Drive this Market

8 3D Cell Culture Market, by End-user8.1 Introduction8.2 Pharmaceutical & Biotechnology Companies8.2.1 Pharmaceutical & Biotechnology Companies Are the Largest End-users of 3D Cell Culture Products8.3 Research Institutes8.3.1 Increasing Government Funding for Research & High Prevalence of Cancer Are Driving Market Growth8.4 Cosmetics Industry8.4.1 Focus on Developing Alternatives to Animal Testing is a Key Factor Driving Market Growth8.5 Other End-users

9 3D Cell Culture Market, by Region

10 Competitive Landscape10.1 Overview10.2 Key Player Strategies/Right to Win10.3 Market Share Analysis10.4 Revenue Share Analysis of the Top Market Players10.5 Company Evaluation Quadrant10.5.1 Stars10.5.2 Emerging Leaders10.5.3 Pervasive Players10.5.4 Participants10.6 Company Evaluation Quadrant: Start-Ups/Smes10.6.1 Progressive Companies10.6.2 Starting Blocks10.6.3 Responsive Companies10.6.4 Dynamic Companies10.7 Company Footprint Analysis10.7.1 Company Product Footprint10.7.2 Company Regional Footprint10.7.3 Competitive Benchmarking of Startup/Sme Players10.8 Competitive Scenario

11 Company Profiles11.1 Key Players11.1.1 Thermo Fisher Scientific, Inc.11.1.2 Merck Kgaa11.1.3 Corning Incorporated11.1.4 Lonza Group Ag11.1.5 Tecan Trading Ag11.1.6 Avantor, Inc.11.1.7 Reprocell Inc.11.1.8 3D Biotek LLC11.1.9 Emulate, Inc.11.1.10 Cn Bio Innovations Limited11.1.11 Synthecon, Incorporated11.1.12 Insphero Ag11.1.13 Kirkstall Ltd.11.1.14 Mimetas Bv11.1.15 Tissuse Gmbh11.2 Other Players11.2.1 Hamilton Company11.2.2 Qgel Sa11.2.3 Lena Biosciences11.2.4 Cellendes Gmbh11.2.5 Uab Ferentis11.2.6 Greiner Bio-One International Gmbh11.2.7 Promocell Gmbh11.2.8 Advanced Biomatrix, Inc. (Part of Bico Group)11.2.9 Visikol, Inc. (Formerly Hurel Corporation)11.2.10 Synvivo Inc.

12 Appendix

For more information about this report visit https://www.researchandmarkets.com/r/v5sl9v

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3D Cell Culture Market by Type, Application, End-user and Region - Global Forecast to 2027 - GlobeNewswire

Cell Biology

Scientists create nanoparticle that helps fight solid tumors – EurekAlert

WINSTON-SALEM, N.C. June 14, 2022 Researchers from Wake Forest University School of Medicine have discovered a possible new approach in treating solid tumors through the creation of a novel nanoparticle. Solid tumors are found in cancers such as breast, head and neck, and colon cancer.

In the study,Xin Ming, Ph.D., associate professor of cancer biology at Wake Forest University School of Medicine, and his team used a nanoparticle to deliver a small molecule called ARL67156 to promote an anti-tumor immune response in mouse models of colon, head and neck, and metastatic breast cancer, resulting in increased survival.

The study is published online in the journalScience Translational Medicine.

Immunotherapy has transformed cancer treatment, but unfortunately, only about 20% of patients respond to treatment.

Most solid tumors have a poor microenvironment that can make them unresponsive to conventional cancer therapeutics, including immunotherapy, Ming said. But this study demonstrates that nanoparticle therapeutics are promising.

According to Ming, the levels of adenosine triphosphate (ATP), an energy-carrying molecule, are high in tumors treated with anti-cancer therapies and quickly degraded into adenosine by a series of enzymes that are highly expressed in the tumors. The presence of adenosine in the tumor microenvironments can contribute to a poor therapeutic response. The compounds like ARL67156 are unable to enter solid tumors alone because of their poor physicochemical properties. However, the nanoparticles design does allow the accumulation and release of ARL67156 selectively in solid tumors.

In the study, scientists used the nanoparticle as a vehicle to deliver ARL67156, an enzyme inhibitor that prevents ATP degradation into adenosine. The nanoparticle was tested in several mouse tumor models.

We found that the nanomedicine substantially suppressed tumor growth and resulted in prolonged survival, Ming said.

Next, researchers tested how the nanoparticle worked in combination with an anti-PD-1 antibody, a common immunotherapy. Researchers noted that the treatment worked well and synergistically with anti-PD-1 therapy.

Finally, scientists evaluated the nanomedicine in a three-dimensional in-vitro model of tumors from patients with colon or breast cancers. Similar effects were observed enhanced tumor cell death through anti-cancer immune response.

Our study suggests theres potential translation of our nanoparticle therapeutic for treating human cancers and that it might also boost the effectiveness of existing treatments, Ming said. These findings warrant further evaluation.

Science Translational Medicine

Animals

8-Jun-2022

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Scientists create nanoparticle that helps fight solid tumors - EurekAlert

Immunology

Dried samples of saliva and fingertip blood are useful in monitoring responses to coronavirus vaccines – EurekAlert

Based on an antibody study, dried samples of easily self-collected saliva and of blood drawn from the fingertip could be useful for monitoring peoples immune responses to vaccination.

In a study by the University of Helsinki and HUS Helsinki University Hospital, the levels of antibodies associated with the SARS-CoV-2 virus were analysed in more than 1,200 employees in the social welfare and healthcare sector to determine whether there were differences in different antibody classes according to viral exposure. Dried saliva and blood samples collected between January and March 2021 were utilised in the study. The exposure and background data were collected using a questionnaire.

Based on the results, immunoglobulin G (IgG) has a 99.5% sensitivity and 75.3% specificity to distinguish people with two vaccinations from non-exposed and exposed individuals, individuals with previous Covid-19 infection, and those with one vaccination. IgG measured from saliva also had an 85.3% sensitivity and 65.7% specificity in distinguishing people with two vaccinations from the other groups.

The results of the study have been published in the Medical Microbiology and Immunology journal.

The study attested to the exposure of social welfare and healthcare employees to coronavirus, visible in the results as elevated antibody levels. A total of 47.5% of nurses and 47.7% of doctors were seropositive due to either a previous infection, vaccination or exposure, whereas only 8.7% of dentists had been exposed to the virus. In addition to dentists, the lowest antibody levels were observed in administrative staff and social workers.

The highest antibody levels in both the blood and saliva were found in those who had both had Covid-19 and had been vaccinated. The lowest antibody levels were seen in individuals who had not been exposed to the virus, who had not had a previous infection and who had not received a vaccination.

Against our expectations, there have been fewer coronavirus infections and instances of exposure among dental care staff compared to, for example, hospital doctors, even though a lot of aerosol-producing procedures are carried out close to the patient in dental care, researcher Laura Lahdentausta says.

At the time of sample collection, the dental care staff had also received the lowest number of coronavirus vaccines, which was reflected in their antibody levels.

Another goal of the study was to develop research methods. In fact, the study provides important information on the use of saliva in the determination of antibody levels.

Based on the results, dried samples reliably reveal antibodies associated with the virus, says Professor Pirkko Pussinen.

The benefit of dried saliva and fingertip blood samples is that they are easy to collect. Samples can be taken at home outside laboratory conditions. Their collection is inexpensive and, in the case of saliva samples, non-invasive.

In the future, this assay technique based on dried spot samples could be effectively utilised to monitor both the immune response produced by vaccination and the need for vaccines in large patient populations, Pussinen adds.

Original article: Lahdentausta L, Kivimki A, Oksanen L, Tallgren M, Oksanen S, Sanmark E, Salminen A, Geneid A, Sairanen M, Paju S, Saksela K, Pussinen P, Pietiinen M. Blood and saliva SARS-Cov-2 antibody levels in self-collected dried spot samples. Medical Microbiology and Immunology. Doi 10.1007/s00430-022-00740-x

Medical Microbiology and Immunology

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People

Blood and saliva SARS-Cov-2 antibody levels in self-collected dried spot samples

13-Jun-2022

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Immunology

DE Shaw Research Licenses First-in-Class Therapeutic for Immunological Diseases to Lilly – PR Newswire UK

NEW YORK, June 13, 2022 /PRNewswire/ -- D. E.Shaw Research (DESRES) today announced that it has entered into an exclusive global license agreement with Eli Lilly and Company (Lilly) for the clinical development and commercialization of DESRES's program of Kv1.3-targeted therapeutics for the treatment of various immunological and inflammatory diseases.

The lead compound, DES-7114, is an orally administered, highly selective small-molecule inhibitor of the ion channel protein Kv1.3. This first-in-class compound recently completed successful Phase 1 clinical trials in healthy volunteers and has demonstrated efficacy in preclinical models of several chronic inflammatory and autoimmune diseases, including ulcerative colitis, Crohn's disease and atopic dermatitis.

Under the terms of the agreement, Lilly will make an initial payment of $60 million to DESRES, with potential development and commercial milestone payments of up to $475 million, as well as royalties on worldwide sales.

The design of DES-7114 by DESRES was enabled by the use of proprietary special-purpose supercomputers that DESRES developed and constructed to perform ultra-high-speed, atomically detailed simulations of the three-dimensional motion of biologically and pharmaceutically significant molecules. A series of such simulations, in combination with experimental studies, resulted in DESRES's unique understanding of Kv1.3's structural, dynamic, and functional properties, leading to the design of compounds that bind strongly to the target protein while likely avoiding undesirable interactions with other ion channels.

"We're enthusiastic about DES-7114's potential, and are hopeful that it will ultimately have a meaningful impact on the lives of patients throughout the world," said DavidE.Shaw, Ph.D., chief scientist at DESRES. "We're also enthusiastic about teaming up with Lilly, which is one of the global leaders in therapeutics for immunological diseases, and is exceptionally well positioned to carry the compound forward through clinical development and commercialization."

"Kv1.3 inhibition represents a promising new approach in immunology," said AjayNirula, M.D., Ph.D., vice president of immunology at Lilly. "We are particularly excited about DESRES's discovery of DES-7114 because the molecule's properties could translate into significant advantages for addressing unmet patient needs."

About D. E. Shaw Research

D.E.Shaw Research (DESRES) uses advanced computational technologies to understand the behavior of biologically and pharmaceutically significant molecules at an atomic level of detail, and to design precisely targeted, highly selective drugs for the treatment of various diseases. Among its core technologies is a proprietary special-purpose supercomputer that it designed and constructed to perform molecular dynamics simulations more than 100 times faster than the world's fastest general-purpose supercomputers. DESRES uses these machines, together with machine learning methods and other computational techniques, in both internal and collaborative drug discovery programs. For more information, visit http://www.DEShawResearch.com.

ContactMadeleine WeingartenD. E. Shaw ResearchMadeleine.Weingarten@DEShawResearch.com

Logo - https://mma.prnewswire.com/media/1837394/DESRES_Logo.jpg

SOURCE D. E. Shaw Research

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Immunology

A New Era: Creating Defenses Against Disease After COVID-19 – The University of Arizona Health Sciences |

As the vortex of the COVID-19 pandemic consumed the world in 2020, scientists worked at a frantic pace to understand the new virus sweeping the globe. The discoveries surrounding SARS-CoV-2 were impressive not only for the speed in which they took place, but also for the new pathways of research they opened.

To the average person, it looked as though scientists were making daily breakthroughs as spike proteins, antibodies and messenger RNA vaccines became topics of everyday conversation. But revolutionary discoveries are rarely Eureka! moments. Instead, scientific advances are almost always the culmination of research that occurs outside of the spotlight. In the realm of immunology, decades of research on the immune system, the human genome and a multitude of other viruses laid the foundation to quickly unravel the mysteries of SARS-CoV-2 and COVID-19.

The immediate end goal was met when COVID-19 vaccines and treatments became available. But the impact of that research is far from over, according to Deepta Bhattacharya, PhD, keynote speaker at the inaugural University of Arizona Health Sciences Tomorrow is Here Lecture Series. He believes the lessons learned during the COVID-19 pandemic have the potential to change the future of science.

The pandemic has shown us that the tools are out there to make infectious disease far less burdensome, not only in the U.S., but globally, said Dr. Bhattacharya, professor of immunobiology in the UArizona College of Medicine Tucson and BIO5 Institute member. We've shown what our technology can do and what our responses can be, and I don't see any reason to accept the status quo anymore.

One of the pandemics biggest lessons, Dr. Bhattacharya said, is that the basics matter.

When people say the COVID-19 vaccines were developed in record time, they really weren't, Dr. Bhattacharya said. They were built on the backs of decades of research that allowed us to move quickly.

Three decades before an unknown virus surfaced in Wuhan, China, scientists were undertaking a massive endeavor known as the Human Genome Project. The intent was to sequence and map all of the genes 3 billion in total that make up the human genome.

In the beginning, the available technology was unreliable and slow, preventing researchers from sequencing more than a few hundred genes at a time. As technology improved, sequencing rates increased dramatically, and in April 2003, the Human Genome Project succeeded in reading the complete genetic blueprint of a human being.

We've shown what our technology can do and what our responses can be, and I don't see any reason to accept the status quo anymore.Deepta Bhattacharya, PhD

The Human Genome Project was criticized by people who asked, What are we really learning from this? What diseases have been cured by understanding and knowing the human genome sequence? Dr. Bhattacharya said. But it's important not to just focus on immediately translatable outcomes. Think about all of the outcomes that came as a result of that project, some of which undoubtedly were the sequencing technologies.

The same sequencing technologies that unraveled the mysteries of the human genome could be applied to viruses. Fast forward to January 2020, and within weeks of being confronted by an unknown pathogen, scientists sequenced and identified the novel coronavirus they dubbed SARS-CoV-2.

Some of the technologies people criticized for not necessarily having an immediate translational impact, now very obviously did, Dr. Bhattacharya said.

The Human Genome Project started in 1990, but the research that laid the foundation for the COVID-19 vaccines has an even longer history. As early as the mid-1970s, immunologists were studying common coronaviruses that affected other species, including mouse hepatitis virus.

It was, in some ways, thankless work. The researchers were asked, why are you studying this? This is a mouse coronavirus why do you care what disease it causes? Dr. Bhattacharya said. What the pandemic has shown us is that those studies taught us an awful lot in terms of preparedness. From these studies, it turned out that the immune response needed to be aimed at a particular protein that the virus makes called spike.

Identifying the viruss Achilles heel wasnt enough, though. Researchers needed to find a way to engineer the spike protein to create an immune response against the virus. That work happened at the National Institutes of Healths Vaccine Research Center. There, scientists were studying respiratory syncytial virus, which causes severe respiratory infections in children, and another common coronavirus that causes cold-like symptoms.

Once engineered, the spike protein needed to be safely delivered to the cells nucleus without killing the cell. Again, the answer came from research that was decades in the making in this case, messenger RNA (mRNA) research at the University of Pennsylvania.

All of that early work that sort of circuitous path science sometimes takes led us to figure out the perfect solution to generate vaccines and immune responses to emerging pathogens, said Dr. Bhattacharya.

On the scientific front, one of the biggest applications from the pandemic can be found in the immunology that led to the development of the highly effective COVID-19 vaccines.

I think structure-based vaccinology is the wave of the future, said Dr. Bhattacharya, whose primary research focuses on a family of viruses known as flaviviruses, which cause diseases including dengue, Zika, Japanese encephalitis, yellow fever and West Nile. The pandemic really showed the power of that particular approach to actually control the immune system and what it's aimed at. Some of the technologies that came from COVID-19 can absolutely be applied to the flaviviruses, as well.

Dr. Bhattacharya, who hopes to develop an effective vaccine for flaviviruses, says none of the flaviviruses have come close to causing the worldwide destruction perpetuated by SARS-CoV-2, though scientists were surprised by the spread of the Zika virus, which reached epidemic status in Brazil in 2016. Still, no one knows which virus could be the source of the next pandemic.

We don't really know what's going to come next, so that means studying families of not just viruses, but also bacteria and fungi, and building up that broad knowledge base and technology that allows us to move quickly, he said. Prevention and preparedness are worth many tons of cure for infectious diseases.

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A New Era: Creating Defenses Against Disease After COVID-19 - The University of Arizona Health Sciences |