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Seminar A combined optical and atomic force microscope for materials and life sciences research On July 23rd, 2024, Dr. Pham Thanh Tri visited the Research Center for Infectious Diseases and gave an insightful talk about how a combined optical and atomic force microscope can be applied in materials and life sciences research   Dr. Dr. Pham Thanh Tri is an Assistant Professor in Biology Department at Nazarbayev University. Dr. Pham has over 23 years of experience with computational simulations and at least 12 years of experience with live-cell imaging and biophysical measurements using optical microscopes and atomic force microscopy, with a focus on measuring the physical, mechanical and electrical properties of both living and non-living matters at nanometer resolution. He recently established the Mechanobiology Laboratory at NU to investigate changes in mammalian and bacterial cell biophysical properties, viability, and biofilm formation when they interact with therapeutic drugs, antibiotics, nanoparticles, nanomaterials, and material surfaces such as metal implants or polymer scaffolds.His research interests include: Computer simulations and image analysis, light microscopy, atomic force microscopy, cell biophysics, biosensors, nanoparticles, bio/nanomaterials, and their applications in life sciences Seminar group photo Have a look at the summary of Dr. Tri’s talk In this talk, we demonstrated the capabilities of a hybrid optical-atomic force microscope, which has many applications in the fields of materials science and life sciences research. When operating in individual mode, time-lapse imaging, often referred to as live cell imaging, can be utilized to see where a specific organelle or protein of interest is located in a cell or tissue as well as its molecular activity. Membrane fibers and bacterial biofilms can also be observed under an optical microscope by labeling them with a fluorescent dye to determine their shape and size. In contrast to optical microscopy, atomic force microscopy was originally developed to image the morphology of a material surface, using a nano probe to physically scan the surface. Its current capacity, though, far exceeds what was originally intended. It can be used to measure the mechanical, electrical, and magnetic properties of the surface of both living and non-living samples in addition to mapping the surface mophorlogy. In the field of mechanobiology, it has also been utilized recently to measure the biophysical characteristics of cells and tissues in liquid. In a hybrid mode, an atomic force microscope can examine surface characteristics like morphology, adhesion, and stiffness, while an optical microscope provides a clear visualization of the area we are measuring and can reveal the localization or activity of a particular protein of interest through fluorescence emission. We can therefore correlate the molecular activity of the living samples with their biophysical characteristics thanks to this combined setup. During my presentation, I will provide several examples of how this hybrid setup is used extensively in materials and biological sciences research. The study areas include biosensors, gas sensors, photovoltaic solar cells, live cell imaging, bacterial biofilms, mechanobiology, nano/biomaterials, metal alloys, and their interactions with living cells.  

The Second Collaborative Webinar of ASM and RCID – Vietnam Webinar Series Building on the success of the 1st webinar, we would like to invite you to our 2nd webinar. Topic: ?????????? ???????? ??? ?????? ???????? ?Register by filling in the form below (or click here) ?You can also scan the QR code on the attached poster. Loading… You will hear about science sharing and career development from famous Asian-American scientists and Indian scientists returning to build in their homeland. Topic of Webinar No. 1, April 15, 2024, 20.00-22.00 Vietnam Time: Infectious Diseases and Health Sciences. The Webinar is supported by ASM-USA and organized by ASM-Vietnam. Please share this event with those who are interested in the Microbiology industry, especially health microbiology – infectious diseases.#RCID #RCIDwebinar

Seminar Structure based-immunogen design, vaccine development and therapeutic antibody discovery against seasonal and pandemic-potential viruses: lessons from SARS-CoV-2 and a focus on Influenza virus On January 23rd, 2024, Dr. Nguyen Nhat Lam visited the Research Center for Infectious Diseases and gave an insightful talk about his research field: vaccine development. The seminar focused on 03 main topics, including (1) proof of concept for structure-based immunogen design driven the development of COVID-19 vaccine, (2) influenza hemagglutinin (HA) stem nanoparticle, a promising vaccine candidate toward universal flu vaccine and (3) protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase.  Dr. Nguyen Nhat Lam is a postdoctoral researcher at the Molecular Immunoengineering Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, USA.From 2011 to 2014, he participated as a research assistant at the National Research Laboratory of Hepatitis C Virus, Ilsong Institute of Life Science, Hallym University, Korea. In 2015, Dr. Nguyen Nhat Lam joined the Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, USA, where he completed his PhD in 2020.His research interests include: Vaccine design Infectious diseases Molecular Immunoengineering Have a look at the summary of Dr. Lam’s talk Background Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. The two viral surface glycoproteins on influenza virions, hemagglutinin (HA) and neuraminidase (NA), facilitate viral entry and egress from host cells, respectively. Although NA is a key target of licensed antivirals, our understanding of the NA antigenic landscape remains incomplete. Moreover, it has been underappreciated as a target for protective antibodies. Identification of such antibodies targeting the viral NA not only leads to effective medical countermeasures but also provides a blueprint to design vaccines targeting those protective epitopes. Methods We used recombinant N2 NA tetramer probes to isolate memory B cells from two convalescent individuals of H3N2 influenza infection by flow cytometry. NA-specific memory B cells were single-cell sorted and their immunoglobulin genes were sequenced. Immunoglobulins were recombinantly produced and assessed their binding to recombinant N2 NAs derived from various viruses. We also performed functional assays including neuraminidase activity inhibition and virus inhibition assays. Two NA antibodies termed NDS.1 and NDS.3 were also structurally characterized in complex with N2 NA tetramers by using cryo-EM.  Results We show that NA-specific human antibodies that target the underside of the NA globular head domain, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses, and confer both pre- and post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures of two such antibodies in complex with NA reveal non-overlapping epitopes covering the underside of the NA head. These sites are highly conserved among N2 NAs, yet inaccessible unless the NA head tilts or dissociates. Conclusions These functional human mAbs recognize the underside of NA which is thought to be inaccessible, suggesting that NA globular head domain can substantially tilt on the virus surface or its tetramer can dissociate as reported in recent studies to expose the underside epitopes for immune recognition. Our findings identify viable sites of vulnerability on NA and will foster new vaccine/therapeutic approaches. 

Seminar Remodeling the lymphoma microenvironment by targeting protein tyrosine kinases Targeting of B cell receptor-associated protein kinases (BCR-BAK) using specific inhibitors such as ibrutinib (Btk inhibitor) or idelalisib (Pi3kɣ inhibitor) have revolutionized the treatment of B-cell malignancies. BAK is an important signaling factor in the BCR signaling pathway and appears to be involved in the pathogenesis of B-cell lymphoma. During her visit to RCID on December 22, 2023, Dr. Nguyen Phuong Hien shared about the signaling factor BAK, the BCR signaling pathway, and the pathogenesis of B-cell lymphoma. In addition, Dr. Nguyen Phuong Hien also reviewed some research on the role of BAK in the progression of lymphoma, the expression of some BAK in the chronic lymphocytic leukemia TME (CLL-TME) and LYN kinase in the progression of chronic lymphocytic leukemia (CLL). Dr. Nguyen Phuong Hien also proposes new application directions for combination treatment regimens through the remodeling of CLL-TME. ????????? Phuong H. Nguyen is the Group Leader, Laboratory for Tumor-Host Interactions, Department of Internal Medicine I, University of Cologne. She is also the Group Leader of the Career Advancement Program (CAP-19), Center for Molecular Medicine Cologne, University of Cologne. Dr. Hien received her Ph.D. in Hematology from the University of Cologne in 2014 under the supervision of Professor Michael Hallek. She then conducted postdoctoral research and was a Co-Principal Investigator, Department of Internal Medicine I, Center for Molecular Medicine Cologne, University of Cologne. Her research focuses on the fields of hematology, chronic lymphocytic leukemia research, tumor microenvironment in cancer research, precision medicine, and particularly chronic lymphocytic leukemia (CLL). Dr. Nguyen has made significant contributions to the field of cancer research. Her research has helped to elucidate the role of B cell receptor-associated protein kinases (BCR-BAK) in the tumor microenvironment. These insights could lead to the development of new targeted therapies for CLL.

Seminar Carbon nanozyme with enhanced phosphatase activity induces cell cytoskeleton collapse and membrane bursting On December 18, 2023, Dr. Pham Thanh Tri (Assistant Professor in Biology Department at Nazarbayev University) visited RCID and shared about his research relating to Carbon nanozyme. Nanozymes have sparked substantial attention in recent years due to their ease of production, low cost, low toxicity, greater flexibility, high stability, and excellent optical properties. However, the impacts of nanozymes with substantial catalytic activity on cells have not been thoroughly investigated. Here, we investigated the effects of sulfur and nitrogen co-doped carbon nanoparticles (SN-CNPs) with strong phosphatase activity on Drosophila neural stem cells. Live cell imaging and atomic force microscopy were employed to evaluate the influence of SN-CNPs on the physical and mechanical properties of neural stem cells in both intact brain and in primary culture. Our live cell imaging data revealed that SN-CNPs induced hyperactive actomyosin contraction, resulting in actin cytoskeleton separation from the cell membrane and subsequent collapse. Additionally, it caused the depolymerization of microtubules, an increase in cell size, and ultimately the bursting of the membrane. The outcomes of the biochemical experiments revealed that SN-CNPs exhibit strong ATPase and GTPase activities. Thus, our SN-CNPs possessed two crucial biological enzymatic activities commonly observed in cells: ATPase and GTPase activities. Due to elevated level of ATPase and GTPase activities, the cell’s internal osmotic pressure increases, resulting in uncontrolled expansion and ultimately cell explosion. Our atomic force microscopy (AFM) studies also revealed that cells treated with SN-CNPs have much higher cortical stiffness than untreated cells. This study is the first to report the existence of carbon-based nanoparticles that have significant ATPase and GTPase activities, as well as a dual cell-destructive mechanism based on phosphatase activity. This novel class of carbon nanozymes has the potential to be used in cancer therapy. Furthermore, these SN-CNPs demonstrated exceptional antibacterial activity, with MIC values of around 200 µg/mL for the majority of investigated bacterial strains. AFM studies of single bacterial cell revealed that after being treated with SN-CNPs, bacterial cells exhibit significant deformation and increased cortical stiffness. In addition, SN-CNPs also possess several peculiar characteristics, such as high concentration antibacterial action, low concentration bacterial growth stimulation, and enhancement of root branching in Arabidopsis thaliana. As a result, the use of nanoparticles as anti-cancer or anti-cancer drugs carriers raises a number of concerns that will need to be thoroughly investigated before clinical trials can start. Dr. Pham Thanh Tri Biography: Tri T. Pham is an Assistant Professor in Biology Department at Nazarbayev University. He received a Double Degree in Advanced Science (Mathematics & Physics) and Aerospace Engineering from the University of Sydney, Australia. He received a Ph.D. in Computational Biophysics at Monash University, Australia. After stints in the USA and Switzerland (where he received a prestigious award from the Swiss National Science Foundation), he joined Nazarbayev University in August 2019. Dr. Pham has over 22 years of experience with computational simulations and at least 11 years of experience with live-cell imaging and biophysical measurements using optical microscopes and atomic force microscopy, with a focus on measuring the physical and mechanical properties of a single cell. He recently established the Mechanobiology Laboratory at NU to investigate changes in mammalian and bacterial cell biophysical properties, viability, and biofilm formation when they interact with therapeutic drugs, antibiotics, nanoparticles, nanomaterials, and material surfaces such as metal implants or polymer scaffolds.