• Antimicrobial Resistance Interdisciplinary Research Group (AMR IRG)

    A Singapore-MIT initiative creating solutions to address AMR

    The AMR IRG is a translational research and entrepreneurship program that tackles the growing threat of antimicrobial resistance.

    By leveraging talent and convergent technologies across Singapore and MIT together, we aim to tackle AMR head-on by developing multiple innovative and disruptive approaches to identify, respond to, and treat drug-resistant microbial infections. Through strong scientific and clinical collaborations, our goal is to provide transformative, holistic solutions for Singapore and the world.

    Our work About AMR

    The AMR IRG is funded by the National Research Foundation Singapore under its Campus for Research Excellence and Technological Enterprise (CREATE) program.

About AMR

Antimicrobial resistance is a global threat to public health, agriculture and food security.

  • Worldwide healthcare projections estimate an impact of 10 million deaths at a cost of $100 trillion annually by 2050.

    In Singaporean hospitals, currently 30-50% of infections are drug-resistant to one or more antibiotics, resulting in increasingly limited treatment options for many common infections. Antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi and parasites evolve genotypic and/or phenotypic changes that enable them to resist the effect of antimicrobial drugs. AMR renders our current treatment arsenal ineffective.

    The global spread of multi-drug resistant “superbug” infections, together with the emergence of new resistance mechanisms, pose a serious threat to our health system and limit our ability to treat infectious diseases. Likewise, without effective antimicrobials, common medical interventions such as surgery, organ transplantation, cancer chemotherapy and diabetes management will pose increasing risk.

    The global spread of multi-drug resistant “superbug” infections, together with the emergence of new resistance mechanisms, pose a serious threat to our health system and limit our ability to treat infectious diseases. Likewise, without effective antimicrobials, common medical interventions such as surgery, organ transplantation, cancer chemotherapy and diabetes management will pose increasing risk.

    The development pipeline for new drugs cannot keep pace with increasing rates of rapidly evolving resistance. We need new innovative approaches to combat antimicrobial resistance and the SMART AMR IRG aims to address this need.

  • Our Director for Research, Dr Wilfried Moreira, spoke recently about the threat of antimicrobial resistance at the One North Festival 2018, an annual immersive public event and celebration of research, innovation, creativity, and enterprise.

    play_circle_filledWatch the video

Who we are

People

Our unique team comprises scientific talent across multiple institutes, continents, and disciplines.

Who we are

People

Co-lead Principal Investigators

Peter C Dedon

PhD MD Biological Engineering


Next

Who we are

People

Program Directors

Megan McBee

Ph.D., Scientific Director


  • meganmcbee@smart.mit.edu

    Originally from the mountains outside of Seattle, Washington, she received her S.B in Chemical Engineering in 2002 from Massachusetts Institute of Technology followed by a Ph.D. in Molecular and Systems Bacterial Pathogenesis from the Department of Biological Engineering in 2007. During her research career, primarily at MIT and SMART, she worked on a diverse array of projects from mucosal immunology to bacterial persistence and translational control. Her research projects utilized several in vitro culture as well as animal models with the ultimate goal of identifying disease- or pathogen-specific cellular or molecular markers of inflammation and bacterial persistence. Most recently, as the first employee and Associate Director at Tychan Pte Ltd, a local Singapore biotechnology company focused on rapid development of antibody therapeutics to emerging infectious diseases, she saw two monoclonal antibodies through all aspects of preclinical development and manufacturing to IND filing for first-in-human safety trials in Singapore within 3 years.

  • RESEARCH & TRANSLATIONAL INTERESTS

    • Infectious Disease and Immunity
    • Therapeutics and Vaccines
    • New Ventures
    • Regulatory Affairs
    • Preclinical Product Development

    AMR IRG projects include making an impact in global health, particularly related to infectious diseases, has been the driving motivation in Dr. McBee’s career and research over the past 15+ years. As such, her primary aim as AMR Scientific Director is to promote and facilitate the research into translational and entrepreneurial projects and ultimately start-ups.

    LINKS

    PREVIOUS
    Next

Who we are

People

Program Directors

Wilfried Moreira

Ph.D., Director, Research; Principal Investigator


  • wilfried@smart.mit.edu

    Wilfried holds a PhD in Microbiology and Immunology from Laval University in Canada during which he was a Fellow of the Strategic Training Program in Microbial Resistance from the Canadian Institute of Health Research. His PhD work focused on antimicrobial mode of action and resistance mechanisms. He subsequently joined the National University of Singapore and the SPRINT-TB program where he led antibiotic discovery projects targeting M. tuberculosis. Wilfried joined the Singapore-MIT Alliance for Research and Technology where his group research focuses on antibiotic resistance mechanisms, novel vulnerable pathways and therapeutic approaches to antibiotic-resistant bacteria.

    Our comprehension of antibiotic resistance mechanisms has changed dramatically over the last decade and moved beyond the one antibiotic/one target/one mechanism of resistance canonical model. Wilfried’s AMR IRG projects include systems biology and genetic engineering approaches to understand and target AMR. Wilfried has also developed a bacteriophage screening and engineering platform. As AMR IRG Director, Research, Wilfried aims to foster a collaborative research culture that can better understand and tackle the global threat posed by AMR.

  • RESEARCH

    • Antimicrobial resistance mechanisms
    • Antimicrobial mode of action
    • Phage therapy
    • Synthetic biology
    • Mycobacteria and gram-negative pathogens

    PROJECTS I CONTRIBUTE TO

    LINKS

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Ram Sasisekharan

PhD Biological Engineering


  • Alfred H. Caspary Professor of Biological Engineering and Health Sciences & Technology

    Koch Institute for Integrative Cancer Research

    Skolkovo-MIT Biomedical Engineering Center

    rams@mit.edu

    Professor Sasisekharan has been a professor of Biological Engineering at MIT since 1996 and served as the Director of the Harvard-MIT Division of Health Sciences & Technology from 2008-12. Sasisekharan received his B.S. in Physical Sciences from Bangalore University, his M.S. in Biophysics from Harvard University, and his Ph.D. in Medical Sciences from Harvard Medical School. The Sasisekharan Laboratory employs a multidisciplinary strategy to develop tools to study glycans and proteins with an ultimate goal towards the development of novel pharmacological approaches to alleviate glycan-mediated disease processes.

  • RESEARCH

    • Glycomics
    • mAb Platform Design
    • Infectious Disease
    • Cancer
    • Human Pathophysiology and Therapeutics

    AMR IRG projects encompass engineered antibody-based approaches to target drug-resistant microbes as part of the mAbplatform group (MAPG).

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Eric Alm

PhD Biological Engineering, Civil and Environmental Engineering


  • Director, Center For Microbiome Informatics and Therapeutics

    ejalm@mit.edu

    Professor Alm earned his Bachelors from the University of Illinois (Champaign-Urbana), his Masters from the University of California (Riverside), and his PhD from the University of Washington (Seattle). He held a postdoctoral appointment at the University of California (Berkeley) and Lawrence Berkeley National Lab before joining the faculty at MIT. His research group is an interdisciplinary team of computer scientists, computational biologists, molecular biologists, and microbial ecologists, which develop complementary computational and experimental methods to understand and engineer the human microbiome. The human microbiome plays a key role in human health and disease. Our research is focused on translating basic science discoveries rapidly into the clinic, where they can contribute to better outcomes for patients.

  • RESEARCH

    • Engineering microbial ecology to improve human health
    • Engineering the human microbiome
    • Non-invasive monitoring of human health
    • Environmental surveillance
    • Sewage epidemiology

    AMR IRG projects include the investigation of antibiotic effects on the microbiome and the clinical evaluation of fecal microbiota transplant for the treatment of drug-resistant persistent bacterial infections in the gut.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Timothy Lu

PhD MD, Biological Engineering


  • Associate Professor of Biological Engineering and Electrical Engineering and Computer Science

    timlu@mit.edu

    Professor Lu received his undergraduate and M.Eng. degrees from MIT in Electrical Engineering and Computer Science. Thereafter, he obtained an M.D. from Harvard Medical School and Ph.D. from the Harvard-MIT Health Sciences and Technology Medical Engineering and Medical Physics Program. Prof. Tim Lu joined MIT as Assistant Professor at the Department. of Electrical Engineering and Computer Science in 2010 and obtained a joint appointment at the Department of Biological Engineering in 2012.

    The Synthetic Biology Group (SBG) is focused on advancing fundamental designs and applications for synthetic biology. Using principles inspired by electrical engineering and computer science, we are developing new techniques for constructing, probing, modulating, and modeling engineered biological circuits. Our current application areas include infectious diseases, amyloid-associated conditions, and nanotechnology.

  • RESEARCH

    • Living Functional Materials
    • Synthetic Analog Computation in Living Cells
    • Integrated Logic and Memory in Living Cells
    • Scalable Toolkits for Engineering Transcriptional Regulation
    • Engineered Bacteriophage Therapeutics

    AMR IRG projects include systems-based analyses of microbe and host using a parallel combinatorial genetics approach to define regulators of drug resistance.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Paula T Hammond

PhD, Chemical Engineering


  • David H. Koch Chair Professor of Engineering

    Head of the Department of Chemical Engineering

    Koch Institute for Integrative Cancer Research

    MIT Institute for Soldier Nanotechnology

    hammond@mit.edu

    Professor Paula Hammond received her B.S. in Chemical Engineering from Massachusetts Institute of Technology (MIT) in 1984, and her M.S. from Georgia Tech in 1988 and earned her Ph.D. in 1993 from MIT. Professor Paula Hammond was elected into the National Academy of Engineering in 2017, the National Academy of Medicine in 2016, and the 2013 Class of the American Academy of Arts and Sciences.

    The Hammond research groups at the MIT Koch Institute for Integrative Cancer Research and SMART AMR focus on the self-assembly of polymeric nanomaterials, with a major emphasis on the use of electrostatics and other complementary interactions to generate multifunctional materials with highly controlled architecture.

  • RESEARCH

    • Nanoscale biomaterials to enable drug delivery from surfaces with spatio-temporal control
    • Responsive polymer architectures for targeted nanoparticle drug and gene delivery
    • Self-assembled materials systems for electrochemical energy devices

    AMR IRG projects include the development of tailored antimicrobial nanoparticle drug-carrier systems designed to target, disrupt and eradicate biofilm-associated infections.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Hadley Sikes

PhD, Chemical Engineering


  • Associate Professor

    Head of the Department of Chemical Engineering

    Esther and Harold E. Edgerton Career Development Professor

    sikes@mit.edu

    Professor Sikes received her B.S. from Tulane University in 1997 and earned her Ph.D. from Stanford University in 2003. She was awarded the Burroughs Wellcome Fund Career Award at the Scientific Interface, 2006-2011, selected as the Innovative Young Engineer NAE in 2017, and received the Best of BIOT Award from American Chemical Society (ACS) in 2018.

    The Sikes research groups focus on engineering biomolecular systems to detect and treat disease in new ways. The principles of engineering design are used to support and extend the practice of evidence-based diagnosis and selection of therapy.

  • RESEARCH

    • Biomolecular engineering
    • Applications of redox chemistry
    • Clinical diagnostics
    • Molecular biotechnology

    AMR IRG projects include the design and engineering of diagnostic tests that can distinguish between bacterial and viral infections in the upper respiratory tract or are designed to detect malaria disease using an unambiguous paper-based test.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Jianzhu Chen

PhD, Biology


  • Koch Institute for Integrative Cancer Research

    jchen@mit.edu

    Professor Chen received his B.S degree from Wuhan University in China and a Ph.D. in Genetics from Stanford University in 1990. He was a post-doctoral fellow and then an instructor at Harvard Medical School before he joined the MIT faculty in the Department of Biology. In addition to being a professor at MIT, Dr. Chen is also a co-director of the Center for Infection and Immunity at the Chinese Academy of Sciences. Professor Chen was formerly the Lead Principal Investigator of the Infectious Diseases Interdisciplinary Research Group at SMART from 2008-2017.

  • RESEARCH

    • Molecular and Cellular Immunology in Infectious Disease
    • Cancer Immunotherapy
    • Vaccine Development
    • Humanized Mouse Models

    AMR IRG projects include the understanding and modulation of host immune macrophage responses during persistent bacterial infections.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (MIT)

Jonyoon Han

PhD, Biological Engineering, Electrical Engineering


  • jyhan@mit.edu

    Professor Jongyoon Han received the B.S. degree in the department of physics of Seoul National University, Seoul, Korea, in 1992, and M.S. degree in physics from the same department in 1994. In 2001, he received his Ph.D. from the School of Applied and Engineering Physics, Cornell University, Ithaca, NY. Before joining MIT as an Assistant Professor of Electrical Engineering in 2002, he was a research scientist at Sandia National Laboratories, Livermore, CA where he studied protein microfluidic separation systems. In 2003, he received a second MIT faculty appointment as Assistant Professor of Biological Engineering. He was the recipient of 2003 National Science Foundation (NSF) – Faculty Early Career Development (CAREER) Award, and 2009 Analytical Chemistry Young Innovator Award from American Chemical Society.

    The Han research group at the Research Laboratory of Electronics (RLE) at MIT focus on micro and nanofabrication technologies applied to molecular separation and concentration, biosensing, cell manipulation and separation, neuroscience and technology, and desalination.

  • RESEARCH

    • NMR spectroscopy
    • Biomechanics
    • BioMEMS
    • Microfluidics and Nanofluidics

    AMR IRG projects include the detection and profiling of antimicrobial resistance of low-abundance pathogens in biofluids and the surveillance and monitoring of artemisinin resistance in malaria.

    PREVIOUS
    Next

Who we are

People

Co-lead Principal Investigators

Peter Preiser

PhD, NTU Biological Sciences


  • Professor of Molecular Genetics and Cell Biology

    NTU Integrated Medical, Biological and Environmental Life Sciences

    prpreiser@ntu.edu.sg

    Prof Peter Preiser is the Chair of the School of Biological Sciences and a Professor of Molecular Genetics & Cell Biology at the Nanyang Technological University (NTU). He obtained a B.A. in 1986 and his Ph.D. in Biology in 1991 from the University of Delaware, USA. After his postdoctoral appointment at Worcester Foundation for Experimental Biology, USA, Pr Preiser joined London’s National Institute for Medical Research as a Senior Research Scientist. In 2003 he left London to join NTU’s School of Biological Sciences (SBS) as an Associate Professor and was later promoted to full Professor in 2009.

    The Preiser research group focuses on molecular mechanisms by which the malaria parasite is able to avoid host immunity and adapt to changes in the host cell environment.

  • RESEARCH

    • Malaria pathobiology and immune evasion
    • Plasmodium falciparum and vivax multigene families (rhoptry protein, variant STEVOR antigen, VIR)
    • Identification of drug targets involved in the DNA replication of the plastid DNA of P. falciparum

    AMR IRG projects include defining the epitranscriptomic regulation of artimisinin-induced stress response in the malaria parasite and the surveillance and monitoring of artimisinin resistance in malaria.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Yeo Tsin Wen

PhD, MD, NTU Lee Kong Chian School of Medicine, Tan Tock Seng Hospital


  • yeotsinwen@ntu.edu.sg

    Associate Professor Yeo Tsin Wen graduated from the National University of Singapore, and went on to complete an internal medicine residency at the University of Hawaii as well as an infectious disease fellowship at the University of Utah. He did his PhD at the Menzies School of Health Research and University of Queensland on the treatment and pathogenesis of severe malaria based in Indonesia Papua. Upon completion of his PhD, he worked as a research fellow at the Menzies School of Health Research and as an infectious physician at Royal Darwin Hospital in Australia. In 2016, Professor Yeo Tsin Wen was awarded the Clinician-Scientist Award (CSA) in the Investigator (INV) category from Singapore’s National Medical Research Council (NMRC).

    The Yeo research group at NTU’s Lee Kong Chian School of Medicine focuses on clinical and epidemiological studies of malaria including the three species most prevalent in South East Asia, namely Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi.

  • RESEARCH

    • Infectious Disease and Epidemiology
    • Dengue and Zika Flaviviruses
    • Malaria Parasites
    • Clinical Trials

    AMR IRG projects are in conjunction with the Sikes lab and include the design and engineering of diagnostic tests that can distinguish between bacterial and viral infections in the upper respiratory tract or are designed to detect malaria disease using an unambiguous paper-based test.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Jenny Low Guek Hong

MD, Duke-NUS Programme in Emerging Infectious Diseases, Singapore General Hospital


  • jenny.low@singhealth.com.sg

    Associate Professor Jenny Low received her degree in Medicine (MBBS) from the National University of Singapore in 1998. She attained her MRCP training (Internal Med), at Edinburgh, United Kingdom in 2002. Further on she did her MPH at Bloomberg School of Public Health, Johns Hopkins University in 2009. Dr Jenny Low is a senior consultant with the Department of Infectious Diseases, Singapore General Hospital. She is a founder and co-director of ViREMiCS, a viral and experimental medicine research centre that supports the development and licensing of therapeutics and vaccines through the use of state-of-the-art technologies.

  • RESEARCH

    • Host immune responses to viruses and vaccines
    • Clinical drug trials for Dengue fever
    • Bench to bedside medicine

    AMR IRG projects are in collaboration with the Alm Lab and include the investigation of antibiotic effects on the microbiome.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Kimberly Kline

MPH PhD, NTU Biological Sciences, Singapore Centre for Environmental Life Sciences Engineering (SCELSE)


  • kkline@ntu.edu.sg

    Kimberly was born and raised in the state of North Dakota in the USA. She earned her PhD from Northwestern University and did her post-doc in the laboratory of Scott Hultgren at Washington University in St. Louis in collaboration with Birgitta Henriques-Normark and Staffan Normark at the Karolinska Institute in Stockholm. During that time, Kim was an American Heart Association Fellow, Carl Tryggers Fellow, and NIH K99 recipient. In 2014, Kim was awarded an ICAAC Young Investigator Award by the American Society of Microbiology.

    The Kline research groups are working to understand the bacterial virulence factors that contribute to colonization, biofilm formation, and infection by E.faecalis and related pathogens.

  • RESEARCH

    • Mechanisms of focal virulence factor assembly
    • Gram-positive & Polymicrobial Interactions in UTI and Wound Infection
    • Pathogen-host interactions important during Group A Streptococcus biofilm formation

    AMR IRG projects interrogate biofilm-associated infections from various perspectives including genetic perturbations using parallel combinatorial genetics, by harnessing macrophage responses, through nanoparticle-based biofilm-penetrating therapies, and through analyses of the epitranscriptomic regulation of phenotypic resistance.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

ChuanFa Liu

PhD, NTU Biological Sciences


  • cfliu@ntu.edu.sg

    Associate Professor ChuanFa Liu received his B.S. degree in 1983 from the China Pharmaceutical University and earned his Ph.D. degree in Science and Technology from the Université de Montpellier, France, in 1989. He held postdoctoral positions at The Rockefeller University and Vanderbuilt University Medical Centre in the USA, before an industry position at Amgen Research USA as a research scientist. At NTU, A/Pr Liu is the Deputy Director of the Drug Discovery Centre.

    The main theme of the Liu research group is the chemical biology of biopolymers such as peptides and proteins. Researchers employ organic chemistry and molecular biology principles in combination with modern biophysical and spectroscopic methods to conduct research in several integral parts of peptide and protein science: chemical and biochemical synthesis, structure and de novo design, and medical applications.

  • RESEARCH

    • Peptide- and protein-based human biopharmaceuticals
    • Practical and cost-effective chemical synthesis methods
    • High-throughput structure-function relationship studies

    AMR IRG projects include structural chemistry design and molecule optimization towards the development of novel drug compounds and resistance-reversion therapies.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Mu Yuguang

PhD, NTU Biological Sciences


  • ygmu@ntu.edu.sg

    Associate Professor Mu Yuguang obtained his B.S. in Physics, M.S. in Quantum Chemistry, and Ph.D. in Physics, all from the Shandong University, China. He conducted postdoctoral work in the Physics Department of the University of Freiburg, Germany, as an Alexander von Humboldt Research Fellow, and in Theoretical Chemistry at the JW Goethe University of Frankfurt am Main, Germany. In 2003, Mu moved to Singapore to undertake a Lee Kuan Yew Postdoctoral Fellowship at the School of Biological Sciences, NTU, where he was later appointed Assisstant Professor in 2006. He currently holds the title of Associate Professor in the School of Biological Sciences, NTU, where his research group develop simulation methods and data analytics tools to model biological events such as protein folding and nucleic acid interactions.

  • RESEARCH

    • Peptide and protein folding, unfolding and misfolding
    • DNA dynamics, DNA-protein, DNA-counterions interactions
    • RNA dynamics and folding

    AMR IRG projects include novel antibiotic development based on transient multitarget molecular interactions.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Mary Chan-Park Bee Eng

PhD, NTU Chemical and Biomedical Engineering, Centre for Antimicrobial Bioengineering


  • mbechan@ntu.edu.sg

    Professor Mary Chan obtained her B.Eng (Chem) from the National University of Singapore in 1986 and earned her Ph.D. in Polymer Chemistry from MIT in 1993. Prior to joining NTU in 2001, she worked in the chemical industry. She was formerly a senior technical manager in Sipix Imaging (CA, USA) working on Epaper development. Pr Chan is an elected fellow of the American Institute of Medical and Biomedical Engineering. She is also on the Editorial Board of three international and highly reputed journals: (i) Journal of Biomedical Materials Research: Part A (ii) American Chemical Society Applied Materials and Interfaces and (iii) Polymers for Advanced Technologies.

    Her research groups at the School of Chemical and Biomedical Engineering and the Centre for Antimicrobial Engineering focus of the development of antimicrobial polymers and nanomaterials for the treatment of bacterial infections.

  • RESEARCH

    • Polymer applications in biotechnology and nanotechnology
    • Antimicrobial polymers and hydrogels
    • Carbon nanotubes and graphene dispersion and sorting
    • Printed electronics – surface patterning and modification

    AMR IRG projects are in collaboration with the Hammond Lab and include the development of antimicrobial polymers that can be incorporated into nanoparticle drug-carrier systems for the disruption and eradication of biofilm-associated infections.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Julien Lescar

PhD, NTU Biological Sciences, College of Science


  • julien@ntu.edu.sg

    Associate Professor Julien Lescar obtained his B.Sc (Hons) from Lycee Louis-le Grand Paris, France in 1984 and earned a MSc in Theoretical Physics and a Ph.D. from the University of Paris XI in 1989 and 1993, respectively. Prior to starting his lab at NTU in 2002 in the School of Biological Sciences, he conducted postdoctoral work at Washington University School of Medicine and Institut Pasteur. With over 25 years of experience in X-ray crystallography, Assoc Pr Lescar leads a multi-disciplinary structural microbiology and drug design laboratory.

  • RESEARCH

    • Structural Biology
    • Infectious Diseases
    • Structure-based Drug Design

    AMR IRG projects involve x-ray crystallographic structure determination of bacterial enzymes and small molecule inhibitors as a tool for structure-based drug design towards the development of resistance reversion therapies.

    PREVIOUS
    Next

Who we are

People

Principal Investigators (Singapore)

Eng Eong Ooi

PhD, MD, Duke-NUS Graduate Medical School, Singapore General Hospital


  • engeong.ooi@duke-nus.edu.sg

    Professor Eng Eong Ooi received his B.M.B.S. in 1993 from the University of Nottingham, earned a Ph.D. degree in Molecular Epidemiology from the National University of Singapore in 1998, and received a FRCPath in Virology from the Royal College of Pathologists, UK, in 2013. Currently, he is the Deputy Director of the Emerging Infectious Diseases Programme at DUKE-NUS Medical School and hold Professor appointments at the Department of Microbiology & Immunology and the Saw Swee Hock School of Public Health, National University of Singapore. With Dr Jenny Low, Pr Ooi is a co-director of ViREMiCS, the Viral Research And Experimental Medicine Centre @SingHealth Duke-NUS.

    The Ooi research laboratory aims to address the critical gaps in knowledge in dengue by positioning itself at the interface between clinical epidemiology, virology and immunology. Researchers combine basic virological and virus-host interaction studies with clinical investigations and experimental medicine.

  • RESEARCH

    • Antibody-mediated protection or enhancement of dengue virus infection
    • Epidemiological phenotypes and factors that determine the outcome of infection or transmissibility
    • Vaccine and therapeutics development
    • Clinical Translation

    AMR IRG projects include the investigation of antibiotic effects on the microbiome in conjunction with the Alm Lab and the development of engineered antibodies with the mAbplatform group (MAPG).

    PREVIOUS
    Next

Who we are

People

Xiaolin Wu

Visiting PhD student


  • xiaolinwu@whu.edu.cn

    Xiaolin Wu holds a BSc in pharmaceutical science in Wuhan University and is a Ph.D. student in Molecular Biology in Wuhan University. She started her research in DNA phosphorothioate (PT) modification in Lianrong Wang’s lab since 2013. In Feb 2017, she joined Peter Dedon’s group as a joint Ph.D. student in MIT to further study DNA PT system and DNA sequencing technology under the funding of China Scholar Council. In Feb 2018, Xiaolin moved to SMART to continue her research in Peter Dedon’s group. She is interested in DNA modification and damage study and new DNA sequencing technology.

    Xiaolin’s research is mainly in DNA PT modification, which is a sulfur modification on DNA sugar-phosphate backbone in a wide range of bacteria and archaea. She utilizes the ChIP-seq technology and other newly developed sequencing technology to study the modification protein binding sites and DNA strand break sites on bacteria genome.

  • RESEARCH INTERESTS

    • DNA modification
    • DNA damage
    • DNA sequencing technology

    LINKS

    Next

Who we are

People

Goh Boon Chong

PhD, Research Scientist


  • boonchong@smart.mit.edu

    Dr Goh Boon Chong received his PhD in Physics from University of Illinois at Urbana-Champaign, USA. His doctoral research focused on the molecular mechanisms of host-pathogen interactions and the structural studies of viruses. He was awarded the SMART Scholars Programme for Postdoctoral Research and joined Peter Dedon’s laboratory in 2016. Dr Goh now leads a multidisciplinary project between the Dedon lab, Julien Lescar’s lab at NTU Institute of Structural Biology, and Liu Chuan Fa’s lab at NTU School of Biological Sciences to develop novel antibiotic adjuvants that reverse antibiotic resistance.

    Dr Goh’s research at AMR IRG focuses on developing antibiotic adjuvants that reverse antibiotic resistance in multidrug-resistant bacteria.

  • RESEARCH INTERESTS

    • Fragment-based drug discovery
    • Structural Biology
    • Protein engineering
    • Molecular modeling and simulations

    PROJECTS I CONTRIBUTE TO

    LINKS

    PREVIOUS
    Next

Who we are

People

Cheryl Chan

PhD, Postdoctoral Associate


  • cheryl.chan@smart.mit.edu

    Dr Cheryl Chan is a Postdoctoral Associate in Peter Dedon’s group. She holds an MSc in Infectious Diseases from the University of Basel and National University of Singapore (NUS) and a PhD in Cellular and Molecular Biology from NUS. Cheryl went on to her postdoctoral training at the University of Oxford where she married her interests in cellular dysregulation in disease with a culture adventure. After returning to Singapore, Cheryl continues her research pursuits at SMART where she is focused on translating the understanding of cellular dysregulation in viral pathogenesis to develop novel host-directed antiviral strategies in combating antiviral resistance.

    Cheryl’s project is focused on identifying and targeting novel host factors of the human epitranscriptome – the collection of post-transcriptional modifications in the cell – that are essential for determining successful viral replication versus an effective host cell response during dengue/zika virus infections.

  • RESEARCH INTERESTS

    • Host-pathogen interactions
    • Host-directed intervention strategies
    • Epitranscriptome regulation
    • RNA biology in viral pathogenesis

    LINKS

    PREVIOUS
    Next

Who we are

People

Lee Wei Lin

Research Scientist


  • weilin@smart.mit.edu

    Dr. Lee Wei Lin joined SMART in 2016 when she received the SMART postdoctoral fellowship to work on mechanisms of RNA modification involving phenotypic and genotypic antimicrobial resistance in Enterococci. In recognition of her postdoctoral work on antimicrobial resistance, she was awarded the 2017 Young Investigator Award by the Society of Infectious Disease (Singapore) and Institut Mérieux. Concurrently, with a Young Individual Research Grant (YIRG) that she received from NMRC in 2016, she works on unravelling pathogen-host interactomes in sexually transmitted Chlamydia. She did her undergraduate in National University of Singapore; and with a scholarship from A*STAR, completed her DPhil in Clinical Medicine in Oxford University in 2014.

    RNA, central to the coding, decoding, regulation and expression of genes, play important roles in many aspects of antimicrobial resistance. Various species of RNA constitute important components of gene expression networks for survival upon exposure to antibiotics. Ribosomal RNA (rRNA) are chemical modified in a number of mechanisms that confer resistance to antibiotics. In particular, erm genes which mediate methylation of rRNA to reduce affinity to ribosome-binding antibiotics, are found in a huge proportion of multidrug resistant bacteria. Further, many of these genes that confer antibiotic resistance are horizontally transferred, and require the bacteria to acquire new tRNA genes and/or chemically modify its set of tRNA to effectively translate these genes which are encoded with different codon frequencies. Dr Lee’s work utilizes recent technological advances that enable high throughput profiling of RNA modifications, also known as epitranscriptomics, to enable exploration of (1) how bacteria chemically modifies its ribosomal RNA to reduce binding affinity of ribosome-targeting antibiotics, (2) how bacteria chemically modifies its tRNA to allow it to effectively translate horizontally-transferred genes, and (3) how bacteria chemically modifies various cellular RNA species for survival in the presence of antibiotic stress. This work is targeted at achieving molecular understanding of mechanisms of antibiotic resistance and response for the identification of candidates and pathways that can be targeted to counter antimicrobial resistance.

  • RESEARCH INTERESTS

    • Enterococci
    • Chlamydia
    • RNA modifications
    • Antimicrobial chemotherapy
    • Phenotypic resistance

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Pham Hoang Long

PhD, SMART Postdoctoral Fellow


  • hoang.long@smart.mit.edu

    Pham Hoang Long obtained his PhD in Synthetic Biology from Yong Loo Lin School of Medicine, National University of Singapore. His PhD research focused on developing new synthetic biology platforms to control in vivo mutagenesis mechanisms for rapid evolution of unique cellular phenotypes for industrial and translational applications. In 2018, he joined Timothy Lu’s group at SMART, where he is working on the development of new synthetic biology platforms to discover novel antimicrobial therapeutics from human microbiome.

    Dr Pham’s research at AMR IRG aims to develop synthetic biology platforms to discover novel antimicrobial therapeutics from human microbiome.

  • RESEARCH INTERESTS

    • Synthetic biology
    • Microbiome engineering
    • Genetic circuits
    • Antimicrobial therapy

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Tan Tse Mien

Senior Laboratory Manager


  • tsemien@smart.mit.edu

    Tse Mien (Mien) holds a first Class Honors in Biotechnology from the University of Tunku Abdul Rahman, Malaysia. Following graduation, she worked as a Laboratory Assistant in animal techniques and cell culture at NUS, in the Department of Physiology for 2 years. She joined SMART in 2009 as a Laboratory Technician in the Infectious Diseases (ID) interdisciplinary research group, working on Mycobacteria and progressed to the position of Laboratory Manager in 2010. Mien serves as the safety representative, overseeing safety in ID since 2017. Currently, Mien is the Senior Laboratory Manager and Safety Representative in the Antimicrobial Resistance (AMR) Interdisciplinary Research Group.

    Mien is in charge of managing and maintaining laboratory operations. Together with the facilities director, she works very closely with the researchers in overseeing laboratory, office space and equipment management as well as the organization of seminars and workshops. As the safety representative of AMR, Mien oversees biosafety level 2 operations involving diverse organisms from intracellular parasites, multidrug resistant bacteria to viruses. She contributes to improvement of safety standards as a member of the AMR ESH (Environmental Safety & Health) committee. She also plays an active role in the AMR SIP (Science In Progress) committee, which organizes scientific workshops for the AMR community.

  • INTERESTS AND WORK SCOPE

    • Laboratory operations
    • Laboratory safety
    • Events organization
    PREVIOUS
    Next

Who we are

People

Gnanakalai Shanmugavel

Senior Laboratory Technologist


  • gnanakalai@smart.mit.edu

    Gnanakalai Shanmugavel holds an Master of Pharmacy in Pharmaceutical chemistry from the Tamil Nadu Dr. MGR Medical University, Chennai, India. She works in Professor Peter Dedon’s laboratory at SMART as a Senior Laboratory Technologist.

    Gnanakalai Shanmugavel works on structure-based drug design project between the Dedon lab and Liu Chuan Fa’s lab at NTU School of Biological Sciences to develop novel antibiotic small molecules to treat multi-drug resistant bacteria.

  • RESEARCH INTERESTS

    • Medicinal chemistry
    • nucleoside chemistry
    • Total synthesis of natural products

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Loo Hooi Linn

Senior Laboratory Technologist


  • hooilinn_loo@smart.mit.edu

    Hooi Linn graduated from Universiti Kebangsaan Malaysia (UKM)– The National University of Malaysia, holding a Bachelor degree major in Biotechnology and minor in Management. She joined the Singapore OncoGenome (SOG) Group at IMB A*STAR in 2004. She later joined SMART in 2009 and worked with Humanized Mouse Project under Prof. Chen Jianzhu. Her past working experience including cord blood processing to obtain stem cells for generating humanized mice, molecular biology, animal related work and histology. Currently, her major role is to support the flow facility, cell sorting and provide training for new flow user. She is also the person in charge for confocal microscope and histology (tissue processing, parafilm sectioning, cryosectioning and staining).

  • RESEARCH INTERESTS

    • Flow Cytometry
    • Bacteria
    • Histology
    • Confocal Microscopy

    PROJECTS I CONTRIBUTE TO

    • Multiplex fluorescent assay for bacterial physiological markers
    • Nanoparticle interaction and uptake analysis
    • ROS detection in E. faecalis
    PREVIOUS
    Next

Who we are

People

Nai Rui Si

B.Sc, Lab Technologist


  • ruisi@smart.mit.edu

    Rui Si graduated from NTU School of Biological Sciences in 2016. Her final year project involved validating BioID as a method to screen for potential protein partners of transcription cofactor CRTC1, and she has previously worked at Temasek Life Sciences in a Drosophila neurobiology research lab. She is now working on bacteriophages in SMART AMR under Dr Wilfried Moreira.

    Rui Si is currently working on a bacteriophage platform project that involves isolating and characterising bacteriophages that are able to target various bacterial strains relevant to public health, such as the ESKAPE pathogens.

  • RESEARCH INTERESTS

    • Bacteriophages
    • Antibiotic Resistant Bacteria

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Patthara Kongsuphol

Research Scientist


  • patthara@smart.mit.edu

    Patthara received her Ph.D. in the field of electrophysiology from Regensburg University, Germany. She spent ~7 years in Institute of Microelectronics (IME) A*STAR to develop microelectronic devices for biomedical uses. Her expertise is in the field of Point-of-Care (POC) protein, DNA and RNA sensors development. She has successfully developed high sensitivity electrochemical sensors for detection of, as low as, 1 pg/mL proteins from non-diluted serum and 250 fM DNA. Her other works include development of automated high throughput patch clamp device and microfluidic chip for isolation of fetal cells from maternal blood.

    She is currently working under Sikes’s group to i) develop rapid and high sensitivity assays for Malaria detection, particularly for the common Singapore strains P. vivax and P. knowlesi, and ii) identify panel of biomarkers which could distinguish bacterial from viral infections. In this project high sensitivity assays that can accurately detect bacterial and virus infections will also be developed.

  • RESEARCH INTERESTS

    • Point-of-Care
    • Biosensors
    • Biomarkers
    • Bacterial infections
    • Viral infections

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Peiying Ho

PhD, Research Manager


  • peiying@smart.mit.edu

    Native to Singapore, Dr Peiying Ho holds a BSc in Life Sciences from the National University of Singapore (NUS), a joint MSc from the University of Basel in Switzerland and NUS, and a PhD in Microbiology & Immunology from NUS. Her doctoral work focused on the immune-modulatory effects of environmental mycobacteria on the BCG vaccine. She joined SMART in 2015 as a research fellow to study physiological effects of starvation stress on mycobacteria. Currently responsible for leading interactions between AMR researchers and the Core Technology Team, Peiying facilitates collaborations and manages projects supported by the Core Team and resources.

    Dr Ho is involved in collaborative projects within the AMR IRG. These include elucidating the genetic mechanisms for bacteriophages against Pseudomonas aeruginosa through the use of bacteria mutant libraries, and developing flow cytometry-based methods for measuring bacterial physiological parameters.

  • RESEARCH INTERESTS

    • Bacteria physiology
    • Flow cytometry methods
    PREVIOUS
    Next

Who we are

People

Wang Jin

Research Scientist


  • wangjin@smart.mit.edu

    I specialize in the biochemistry and bioanalytical chemistry of nucleic acids. I earned my BS in chemistry at Wuhan University in 2005, after which I completed my PhD in biochemistry at Hong Kong Baptist University in 2009 under the direction of Prof. Daniel W. J. Kwong. After a postdoc in DNA damage and modifications at UC Riverside (2009-2012), under the direction of Prof. Yinsheng Wang, I joined Prof. Peter Dedon’s research group at SMART as a postdoc and was later promoted to Research Scientist.

    My research at SMART has been focusing on RNA biochemistry, infectious disease, and antiviral drug discovery. Using a systems approach to investigate the roles of RNA cap in stress response, the effects of antibiotics, and antimicrobial resistance.

  • RESEARCH INTERESTS

    • Nucleic acid biochemistry
    • Epigenetics
    • Antimicrobial resistance
    • Infectious disease
    • Drug discovery and development
    PREVIOUS
    Next

Who we are

People

Wenhe Zhong

PhD, Research Scientist


  • wenhe@smart.mit.edu

    Dr. Wenhe Zhong has his PhD in The University of Edinburgh in UK, working on enzymology and structure-based drug discovery for trypanosomiasis. Then he moved to NTU Singapore working in Prof. Daniela Rhodes lab as a postdoc and studied the mechanism of telomerase recruitment. Two years later he awarded the SMART Scholar fellowship in Prof. Peter Dedon lab. Now he is leading the antibiotic drug discovery project through collaborations with investigators at NTU and Experimental Therapeutics Centre (ETC) A*STAR.

    Dr. Wenhe Zhong’s research at AMR IRG involves the development of new antibacterial agents targeting tRNA epitranscriptome by small molecule high-throughput screening (HTS) and structure-based drug design. Dr. Wenhe Zhong also repurposes FDA-approved drugs and clinical molecules as antibiotics or antibiotic adjuvants for the treatment of drug-resistant bacterial pathogens.

  • RESEARCH INTERESTS

    • Anti-infective development
    • Structure-based drug discovery
    • Structural biology
    • Drug repurposing

    PROJECTS I CONTRIBUTE TO

    LINKS

    PREVIOUS
    Next

Who we are

People

Michelle E Turvey

PhD, Research Scientist


  • michelle.turvey@smart.mit.edu

    Dr Michelle Turvey holds a BSc in Biotechnology and a PhD in Microbiology & Immunology from The University of Adelaide, Australia. Her doctoral work was focused on the mechanisms of directed cell migration in metastatic cancer cells and in immune cells during inflammation and autoimmunity. In 2016, she moved to Singapore and joined Paula Hammond’s group at SMART, where she is now responsible for leading a collaborative project between the Hammond Labs based at SMART and MIT, the MBE Chan Lab based at NTU, and investigators at SCELSE and NTU Lee Kong Chian School of Medicine.

    Dr Turvey’s research at AMR IRG involves the development of nanoparticle-based drug delivery systems capable of controlled spatio-temporal release of synergistic drug combinations for the treatment of biofilm-associated microbial infections.

  • RESEARCH INTERESTS

    • Immunity to infectious disease
    • Biomaterials
    • Tailored drug delivery

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Irina Afonina

PhD, Postdoctoral associate


  • irina@smart.mit.edu

    Irina graduated from Saint-Petersburg Technological University (Russia) in 2010 with engineer degree in biotechnology and spent few years in St. Petersburg Pasteur Institute working with antibiotic resistant bacteria. She then moved to Singapore and pursued her PhD in Kimberly Kline’s lab studying relationship between enterococcal adhesins. In 2018 Irina joined SMART AMR-IRG under Timothy Lu and Kimberly Kline supervision as a postdoc.

    Dr Afonina’s work at AMR IRG involves developing combiGEM-CRISPRi technology in Enterococcus faecalis to target biofilm-associated infections.

  • RESEARCH INTERESTS

    • Enterococcus faecalis
    • Combinatorial genetics
    • Biofilms

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Seetharamsingh Balamkundu

PhD, Postdoctoral associate


  • seetharamsing@smart.mit.edu

    Dr. Seetharamsingh holds an M.Sc. Organic Chemistry and he received his Ph.D from National Chemical Laboratory, Pune, India in 2016. His doctoral studies focused on the "Silicon Switch approach of marketed drugs to identify molecules with improved pharmacokinetic properties and total synthesis of biologically active natural products". In 2016 he joined Peter Dedon’s laboratory at SMART as a postdoctoral associate.

    Dr. Seetharamsingh works on structure-based drug design project between the Dedon lab and Liu Chuan Fa’s lab at NTU School of Biological Sciences to develop novel antibiotic small molecules to treat multi-drug resistant bacteria.

  • RESEARCH INTERESTS

    • Medicinal chemistry
    • Nucleoside chemistry
    • Total synthesis of natural products

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Xinlei Qian

PhD, Senior Postdoctoral Associate


  • xinlei@smart.mit.edu

    Dr. Xinlei Qian obtained her PhD in Microbiology from University of Massachusetts at Amherst, USA. Her doctoral work is about c-type cytochromes involved in electron transfer in gram negative bacteria Geobacter sulfurreducence. During the following years, Xinlei switched her research interests into the area of nucleic acid interacting proteins and antibodies targeting infectious disease.

    Dr. Xinlei’s project at AMR IRG focuses on structural characterization of antibody targeting infection disease.

  • RESEARCH INTERESTS

    • Antibody characterization
    • Bi specific Fc
    • Fc effector

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Abdul Rahim Mohamed Sharif

Senior Research Engineer


  • sharif@smart.mit.edu

    Sharif holds a B. Tech in Biotechnology from SRM University, India and M.Sc. in Biomedical Engineering from Nanyang Technological University, Singapore. His Master’s thesis was focused on developing a photopolymerized antimicrobial hydrogel coating for biomedical devices. He joined Paula Hammond’s Lab at SMART in 2012 and collaboratively conducts research with post docs, research scientist and clinicians in various research projects developing biomaterials for therapeutic applications.

    Sharif’s research at AMR-IRG involves developing liposomal nanoparticles to combat antimicrobial resistant bacteria by utilizing layer-by-layer technology.

  • RESEARCH INTERESTS

    • Biomaterials
    • Drug delivery
    • Nanotherapeutics

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Sundar Prasanth Authimoolam

Postdoctoral Associate


  • sundarprasanth@smart.mit.edu

    Sundar Prasanth Authimoolam holds a BTech in Chemical Engineering, Anna University, Chennai, India, and MS, PhD in Chemical Engineering from University of Kentucky, Lexington, United States. His doctoral work was on developing synthetic mucin mimics from drug encapsulated polymeric nanostructures. He also holds an industrial experience as Chemical Process Engineer in Bharat Petroleum Corporation Ltd., Mumbai, India. He previously worked as a postdoctoral researcher in NewYork University in Abu Dhabi. In 2018, he joined Paula Hammond’s Group at SMART, and works in a collaborative project between the Hammond Labs based at SMART and MIT, the MBE Chan Lab based at NTU, and investigators at SCELSE and NTU Lee Kong Chian School of Medicine.

    Dr Sundar’s research at AMR-IRG involves development of drug delivery systems such as polymeric nano/microcarriers, hydrogels, and thin film coatings via Layer-by-layer self-assembling approaches in forming functional materials for antimicrobial resistance.

  • RESEARCH INTERESTS

    • Biomaterials
    • Drug delivery
    • Polymers
    • Nanomaterials
    • Pharmaceuticals

    PROJECTS I CONTRIBUTE TO

    PREVIOUS
    Next

Who we are

People

Ameya Sinha

Graduate Student


  • ameya1@e.ntu.edu.sg

    Originally from Bombay, Ameya graduated from Nanyang Technological University, Singapore with a B.Eng in Bioengineering. Having previously worked on the mechanobiology of red blood cells, he transitioned to working with Plasmodium parasites under the collaborative supervision of Peter Dedon at MIT and Peter Preiser at NTU. When not holed up in the mass spectrometry room or next to the coffee machine, he can be found meandering through the city looking for the best food that Singapore has to offer.

    Ameya’s research at AMR-IRG revolves around deciphering the Plasmodium epitranscriptome as a mechanism of translational control. Leveraging the mass spectrometer as an omnipotent tool, he aims to provide a glimpse of the DNA, RNA and the proteome of the Plasmodium falciparum parasite at a systems-level.

  • RESEARCH INTERESTS

    • Plasmodium Biology
    • DNA and RNA modifications
    • Omics-based approaches

    PROJECTS I CONTRIBUTE TO

    LINKS

    PREVIOUS

Our work

The AMR IRG approach

Our projects within the AMR IRG range from fundamental microbiology through the understanding of resistance mechanisms and host-pathogen relationships, to the development of novel diagnostics and therapeutics that can be progressed towards clinical translation.

Projects

Our work

  • Combinatorial genetics approach to prevent and disrupt biofilm-associated infection

    New scientific technologies continue to advance and can be leveraged to define drug resistance mechanisms from the perspectives of both the microbe and the host.

    In this project, the team will use parallel combinatorial genetics to systematically identify combinations of novel regulators of drug resistance. The Lu lab has developed CombiGEM CRISPR (CGC) to screen and identify novel gene combinations in human immune cells having activity against tuberculosis and shigellosis.

    The key requirements for the application of this system to Enterococci are (1) the ability to perform CRISPR-mediated gene editing, (2) the availability of inducible promoters and efficient DNA delivery systems, and (3) a robust and reliable host-pathogen infection system to screen and then validate gene perturbations. With the recent report of efficient CRISPR editing in Enterococci, the Lu lab expertise in CGC, and the Kline lab genetic toolbox and biofilm model systems, this team is poised to apply CGC for the first time to a Gram-positive pathogen in the context of biofilm-associated host-pathogen interactions.

      Next
  •  

Our work

  • Enhancing macrophage reactivity for effective elimination of microbes

    MIT Investigator Jianzhu Chen (Biology), Singapore Co-Investigator Kimberly Kline (NTU, Biological Sciences), Mark Veleba (Postdoctoral Associate)

    The traditional direct targeting of microbes with antibiotics is now being challenged by emergence of antibiotic resistance.

    We propose to augment host immunity by enhancing the anti-microbial activity of macrophages using compounds identified in screens of a large chemical library. The team will focus on E. faecalis infection, which suppresses macrophage activation in vitro and in vivo. Combination therapies that target both microbes and host immunity shouldmore efficiently eliminate pathogens and reduce the risk of developing drug resistance, while immune stimulants should be effective with drug-resistant bacteria such as vancomycin-resistant Enterococci (VRE)

      Previous
      Next
  •  

Our work

  • Antibody development for targeting drug-resistant microbes

    MIT Investigator Ram Sasisekharan (Biological Engineering), Singapore Co-Investigator Eng Eong Ooi (DUKE-NUS Medical School), Yok Teng Chionh (Research Scientist), Xinlei Qian (Senior Postdoctoral Associate), Jinling Fang (Principal Laboratory Technologist), Yun Rui Tan (Senior Laboratory Technologist), Hui En Jannah Lim (Laboratory Technologist), Yuzhou Yang (Laboratory Technologist)

    The mAbplatform group (MAPG) aims to leverage its antibody engineering technology to address key challenges in AMR by developing novel antibody-based approaches to target drug-resistant microbes.

    In this context, the MAPG will establish a comprehensive antibody development platform that will include (i) production of high quality mabs, (ii) functional characterization of mabs, both at the level of target engagement, as well as its Fc-related effector functions, and (iii) analytical characterization to enhance ‘developability’ of mAbs in the context of clinical use. Based on mAbs developed under the Zika Program, we will focus our efforts on leveraging this platform for rapid development and testing of mAbs against anti-microbial targets both in the context of conventional antibody formats as well as novel formats with enhanced target binding functionality such as Bi specific mAbs, Dual Variable Domain Immunoglobulins (DVD-Ig) or with modified Fc effector functions for enhanced half-life in circulation or enhanced opsonophagocytic activity. In parallel, MAPG is exploring novel strategies for establishing stable antibody producing cells lines for rapid translation and drug development.

      Previous
      Next
  •  

Our work

  • Effects of clinically relevant antibiotics on the microbiome

    MIT Investigator Eric Alm (Biological Engineering), Singapore Co-Investigator Eng Eong Ooi (Duke-NUS Medical School), Jenny Low (Singapore General Hospital), Andrea Kwa (Singapore General Hospital), Shirin Kalimuddin (Singapore General Hospital), Raphael Zellweger (Duke-NUS Medical School), Thuan Tong Tan (Singapore General Hospital)

    Despite the enormous interest in the commensal gut microbiome, surprisingly few studies have followed the effects of antibiotics on the commensal microbiome. Moreover, little is known about the extent to which antibiotic sensitivity or resistance is affected by interaction with the human host and other factors, including diet.

    In this project, we will characterize the effects of an antibiotic regimen commonly used in Singaporean clinical practice on the microbiome. Antibiotic effects will be tracked in vivo in a small cohort of human patients, ex vivo in fecal material collected from those patients prior to antibiotic treatment, and in ex vivo assays combined with a variety of dietary substrates.

      Previous
      Next
  •  

Our work

  • Biofilm-penetrating systems for novel therapeutic delivery

    Many bacterial pathogens have evolved to adapt and survive in hostile environments such as pulmonary mucus and biofilms for Pseudomonas aeruginosa and MRSA infections. These environments are not only highly protective in terms of drug penetration, but the bacteria also enter a state of phenotypic antibiotic tolerance, greatly slowed metabolism, expression of drug efflux pumps, excretion of drug-degrading enzymes, and generation of biofilms that block penetration of small molecule drugs. The effect of such environments is to act as a route toward the generation of more resistant strains, while preventing response of the existing bacteria to treatment.

    The goal of this project is to develop novel therapeutics that overcome these barriers. Specifically, we will generate novel layer-by-layer (LbL) nanoparticles designed to contain a range of water-soluble and insoluble drugs within a nanocarrier core surrounded by alternating charged layers of poly-cation and –anion that are selected for their ability to penetrate into and transport through biofilms. Attached to these nanoparticles will be novel therapeutics developed in the Dedon, Lu and Chan labs. Characterization of these systems will utilize models and methods developed at NTU in the Kline lab, and provide opportunities for further collaboration with additional members of the Singapore infectious disease community, including Kevin Pethe (LKCSM, NTU).

      Previous
      Next
  •  

Our work

  • The role of the epitranscriptome in antimicrobial resistance in malaria parasites

    Over the past decade, we have discovered a system of translational control of gene expression in all living organisms, involving dozens of RNA modifications – the epitranscriptome – coupled with an alternative genetic code of synonymous codon usage. Profs. Preiser and Dedon have defined the set of RNA modifications in Plasmodium falciparumand identified two epitranscriptome behaviors in the red blood cell life cycle of the parasite. One involves simultaneous up-regulation of ~20 modifications during the maturation of the parasite, in concert with developmental up-regulation of protein production and metabolism in general. The other facet of epitranscriptomic behavior involved the model for translational control of gene expression. Analysis of proteome and tRNA modifications across the RBC life cycle revealed coordinated up-and down-regulation of tRNA isoacceptors and proteins coded by genes enriched with the cognate codons of these tRNAs.

    Building on these observations, preliminary analyses show stress-specific reprogramming of the epitranscriptome, including patterns unique to exposure to antimicrobial agents such as artemisinin. We now propose to define the role of translationalcontrol mechanisms in the emerging resistance to artemisinin in malaria parasites in Southeast Asia. Mutations in the kelch K13 gene were identified in artemisinin-resistant clinical isolates in SE Asia, while kelch mutations and artemisinin resistance have not emerged in Africa, which raises questions about the potential for other parasite mechanisms to play a role in artemisinin resistance. Here we will define one such mechanism: a link between tRNA modifications, an alternative genetic code, and artemisinin resistance in P. falciparum. Using wild-type and kelch mutant P. falciparum strains, we will quantify changes in tRNA modification, protein, and transcript levels during the RBC life cycle. Preliminary studies are consistent with the idea that strains with kelch-mediated artemisinin resistance prefer a metabolically and translationally "less active" state when encountering artemisinin stress and respond by down-regulating the general tRNA modification levels that would normally increase during the RBCphase of parasite development. We propose to characterize these pathways to identify potential targets for therapeutic intervention to reverse the drug resistance.

      Previous
      Next
  •  

Our work

  • Epitranscriptome-based antibiotics and resistance-reversing adjuvant therapies

    MIT Investigator Peter Dedon (Biological Engineering) Singapore Investigators Kimberly Kline (NTU, Biological Sciences), Julien Lescar (NTU, Biological Sciences), Chuan Fa Liu (NTU, Biological Sciences)
    Research team members Bo Cao (Research Scientist), Kalyan Kumar Pasunooti (Research Scientist) , Wenhe Zhong (Research Scientist) , Boon Chong Goh (Research Scientist), Seetharamsingh Balamkundu (Postdoctoral Associate), Cheryl Chan (Postdoctoral Associate) , Vinod Kumar Gadi (Senior Laboratory Technologist), Ramesh Neelakandan (Senior Laboratory Technologist), Gnanakalai Shanmugavel (Senior Laboratory Technologist), Wei Lin Lee (SMART Scholar)

    All forms of RNA in all organisms are chemically modified on the nucleobase and sugar moieties, with these RNA modifications – the epitranscriptome – emerging as critical players in bacterial pathogenicity. For example, many bacterial pathogens respond to the stresses of infection and antibiotic treatment with a genetically-programmed entry into a slowly-or non-replicative state accompanied by the formation of a biofilm or, in the case of mycobacteria, a granuloma. The bacteria in this state are typically resistant or tolerant to a broad range of antibiotics (i.e., persistent), with the bacteria reverting to a drug-sensitive state upon removal of the stress. Here we propose to develop resistance-reversing adjuvant drugs that target the RNA-modifying enzymes.

    This project builds on our successful development of tRNA methyltransferase inhibitors as antibiotic candidates, making use of an antibiotic development platform created over the past four years. The first target for drug development will be the ribosomal RNA (rRNA) methyltransferases that confer innate and phenotypic resistance to macrolide antibiotics such as erythromycin (ERY). ERY binds to the 23S rRNA at the ribosomal peptide exit tunnel, which stalls translation. ERY resistance methyltransferases (Erm) methylate key nucleotides at the ERY binding site and block drug binding. For example, ErmB is an inducible enzyme that methylates A2058 in 23S rRNA in Ef, S.pneumoniae, and S. aureus, while the analogous Erm37 in M. tuberculosis (Mtb) is constitutively expressed, rendering Mtb innately resistant to ERY. We propose to target ErmB and Erm37 for development of resistance-reversing adjuvant drugs by structure-based design and screening-based discovery in collaboration with microbiologist Kimberly Kline, structural biologist Julien Lescar and medicinal chemist Liu Chuan Fa.

      Previous
      Next
  •  

Our work

  • The role of the epitranscriptome in bacterial biofilms and phenotypic antibiotic resistance

    Many bacterial pathogens respond to the stresses of growth, infection and antibiotic treatment with a genetically-programmed entry into a slowly- or non-replicative state accompanied by the formation of a biofilm or, in the case of mycobacteria, a granuloma. The bacteria in this state are typically resistant or tolerant to a broad range of antibiotics (i.e., persistent), with the bacteria reverting to a drug-sensitive state upon removal of the stress. This persistent state is a major form of antimicrobial resistance (AMR) and is also genetically programmed, but we know exceptionally little about the mechanisms driving persistence. Here we propose to explore the role of RNA modifications – the epitranscriptome –in phenotypic resistance and in the formation of biofilms, focusing initially on two clinically important biofilm-forming pathogens: Entercoccus faecalis (Ef) and Pseudomonas aeruginosa (Pa).

    This project has two objectives. One is to test the hypothesis that Efand Parespond to biofilm-inducing stresses by translationally-controlled phenotypic remodeling. This involves stress-specific reprogramming of dozens of modified nucleosides in tRNAs and rRNAs, which leads to selective translation of codon-biased transcripts for families of genes critical to forming a biofilm and becoming persistent. This work entails genomic analysis of codon usage patterns and LC-MS analysis of tRNA modifications and proteins in Ef and Pa in planktonic and biofilm growth states, using biofilm models and Ef strains developed in Prof. Kline’s lab. We are particularly interested in translational regulation of the variety of drug efflux pump families (e.g., Mex and OprM), which have highly biased codon usage patterns and are likely coordinately regulated by tRNA modifications. The second objective is to define the role of rRNA modifications in drug resistance and biofilm formation, such as the erythromycin resistance methyltransferases (Erm) that site-specifically methylate 23S rRNA to cause drug resistance. This work involves the same approaches and tools used for tRNA analysis.

      Previous
      Next
  •  

Our work

  • Fecal microbiota transplant (FMT) for eradication of carbapenem-resistant Enterobacteriaceae gut colonization: a pilot, randomized-controlled trial

    Carbapenem-resistant Enterobacteriaceae is one of the three critical-priority antimicrobial-resistant threats in the latest 2017 WHO priority threat list and is a growing threat in Singapore with rising incidence since 2010. There are currently widely accepted clinical options for decolonizing carriers, creating strain on the healthcare system and restricting access to healthcare for a large number of patients.

    In this project, we aim to test whether fecal microbiota transplantation (FMT) is effective in reducing the gut bacterial load of the two main forms of CREs: Cohort 1 -Carbapenem-producing Enterobacteriaceae (CPE); and Cohort 2 -Non-carbapenem carbapenem-resistant Enterobacteriaceae (NCP-CRE). Subjects will be followed using microbiome profiling including 16S and metagenomic sequencing, as well as culture-based approaches. Genomic data will be used to interrogate the mechanism as well as the dynamics of decolonization. In addition, we will test the specific hypothesis that CPE patients will be more effectively and rapidly decolonized by FMT, due to a stronger fitness trade-off in the absence of antibiotics. Results from this study will be used to scale up to larger cohorts.

      Previous
      Next
  •  

Our work

  • Design of a diagnostic test for bacterial versus viral upper respiratory infections

    Singapore's National Strategic Action Plan on AMR emphasizes the need to ensure the appropriate use of antimicrobials in order to curb the spread of AMR. Antimicrobials are often prescribed before an individual's infection has been diagnosed. Accurate, rapid diagnostics have been identified as a pressing need. While panels of biomarkers for distinguishing bacterial from viral infections have been proposed and tested, success with this approach has not been satisfactory. We will leverage bead-based assays that rapidly and affordably provide aM to fM sensitivity in order to test the hypothesis that enhanced sensitivity may yield lower incidences of false positives and false negatives. In a parallel effort, we will simultaneously mine large, existing data sets to discover new candidate biomarkers that can distinguish bacterial from viral infections.

      Previous
      Next
  •  

Our work

  • An unambiguous paper-based test for malaria

    Current colorimetric rapid tests for malaria can be difficult to interpret correctly when protein biomarkers are present in blood at low abundances. We have produced prototype tests for malaria caused by Plasmodium falciparum that exhibit enhanced thermal stability and unambiguous colorimetric readouts in comparison with existing tests. We will conduct validation studies using clinical samples, including side-by-side testing with gold standard, PCR-based methods. We will also extend the concept to produce tests that diagnose malaria caused by P. vivax and P. knowlesi.

      Previous
      Next
  •  

Our work

  • Antimicrobial resistance profiling of low-abundance pathogens in biofluids

    Isolation and identification of bacteria from bacteria-infected blood are often hindered by extremely low abundance (~1-5 CFU/ml) and presence of large molecular and cellular backgrounds, so bacterial diagnosis has been mainly dependent upon blood culture followed by phenotypic assay. However, culture analysis takes a long time (more than 48 hours) during which indiscriminate use of broad-spectrum antibiotics lead to increased antibiotic resistance and collateral damage to normal gut fauna with adverse effects. Rapid assays to detect pathogen directly from blood have been reported, but these assays have limited sensitivity and specificity due to host contamination, and can only target a limited panel of pathogens, so they have yet to be successful in changing clinical practice. We would like to address this problem by proposing a rapid, culture-free workflow for identification of a wide range of bacteria from blood with very low abundance of bacteria, which is made possible by use of our spiral microfluidic sorter and novel digital PCR technology.

      Previous
      Next
  •  

Our work

  • Monitoring artemisinin resistance in malaria via functional measurements

    Artemisinin-resistant malaria parasites, which emerged within the last decade in Southeast Asia, threaten the efficacy of the current standard of care for malaria. Conventional methods to detect artemisinin-resistant parasites are either too time-consuming or with limited specificity, or both. Previous MIT-NTU collaboration on malaria parasite detection and resistance generated many promising, functionally-relevant modalities of detecting parasite resistance early (within 24 hours), in order to provide actionable information for better clinical management.

    In this project, we will continue developing these technologies, with the goal of implementing a system that are readily deployable on the field, with minimal needs for research and manpower infrastructures.

      Previous
      Next
  •  

Our work

  • A bacteriophage screening and engineering platform

    Singapore Lead Investigator Wilfried Moreira (AMR IRG) Research team members Rui Si Nai (Laboratory Technologist)

    Infections and other detrimental effects caused by bacteria pose major challenges to human and animals health and modern medicine practices, plant and animal agricultural production as well as food processing and manufacturing. On the other hand, the microbiome, the population of bacteria that inhabit a healthy human or animal body, is essential to their health. Antibiotics or sanitizing agents used to control harmful bacteria do not discriminate between good and bad bacteria. In addition, harmful bacteria are becoming increasingly resistant to these antibacterial molecules. An alternative solution is required for selective bacterial control. Bacteriophages or phages are bacterial viruses found nearly everywhere in the environment that infect and kill bacteria. They have been used for over a hundred years as what is known as phage-therapy. The shortage of newer antibacterial molecules and the rise of antibiotic resistance has revived the interest in these natural bacterial killers.

    We have developed a phage screening and engineering platform. This platform enables the isolation and screening of phages that selectively infect bacterial pathogens. Isolated phages are amplified and purified. We are also genetically engineering phages to enhance their antibacterial properties and facilitate their purification. This platform-technology can deliver a phage-based solution to areas where bacteria control is critical and where current solutions are either scarce or inadequate such as surface decontamination, animal health and agricultural production or consumer health and human medicine.

      Previous
      Next
  •  

Our work

  • Systems biology and genetic engineering approaches targeting antibiotic resistance

    Singapore Lead Investigator Wilfried Moreira (AMR IRG)
    Research team members Jacqueline Chen (Laboratory Technologist)

    We use systems biology approaches combined with genetic engineering to identify and characterize novel pathways involved in antibiotic resistance in pathogenic bacteria. For example, the production of hydrogen sulphide (H2S) in bacteria has been associated with sensitivity to antibiotics with very different mechanisms of action. We have shown that H2S is produced by mycobacterial species such as Mycobacterium bovis (M. tuberculosis surrogate), as well as emerging pathogen like Mycobacterium abscessus. In these bacteria, H2S is associated with multi-drug resistance. Inhibition of the H2S biosynthetic pathway sensitizes the bacteria to several antibiotics. On the other hand, in bacterial species like Acinetobacter baumannii that does not produce H2S, we showed that exogenous H2S sensitizes the bacteria to multiple antibiotics by several orders of magnitude. We are now asking the question: What effect does H2S cause to bacterial system that leads to antibiotic resistance or sensitization? To answer this question, we employ system’s biology tools such as transcriptomics, proteomics, and phenotypic characterization of H2S treated bacteria. Moving foward, we are looking at validating these findings in animal models of infection with the objective of translating them into an antibiotic-sensitization strategy targeting multi-drug resistant clinical isolates.

      Previous
  •  

Our facilities and resources

Your project. Our support.

The AMR IRG Core Technology Team can provide support based on a collaborative consultation model where projects can be user-driven for technology use or Core Team-driven for methods development projects.
To discuss a project with Dr Peiying Ho, our Research Manager for Core Technology Platforms, get in touch.

Our facilities and resources

People and expertise

  • Dr Peiying Ho

    Research Manager, Core Technology Team and Resources

    peiying@smart.mit.edu

  • Dr Cui Liang

    Research Scientist

    Mass Spectrometry Facility

  • Ms Hooi Linn Loo

    Senior Laboratory Technologist

    Flow Cytometry Facility

  • Ms Lan Hiong Wong

    Senior Laboratory Technologist

    Laboratory Animal Services

  • Ms Faeqa Binte Muhammad Rajaie Fizla

    Laboratory Technologist

    Microbiology

  • Ms Nah Qian Hui

    Laboratory Technologist

    Microbiology

Careers

Open positions

We're accepting applications to the positions below.

PhD Fellowship Postdoctoral Fellowship
  • Laboratory Technologist (6 months contract)

    IRG_AMR_2018_013

    Job description

    The Antimicrobial Resistance Interdisciplinary Research Group (AMR IRG) of the Singapore-MIT Alliance for Research and Technology is seeking a full-time Laboratory Technologist to join a dynamic team working on antibacterial drug resistance mechanisms. The length of appointment is for 6 months.

    Responsibilities

    • · Conduct experiments on antibiotic resistance mechanism projects
    • · Analyze, troubleshoot and report experimental results
    • · Keep track of and maintain lab-wide inventory and stocks
    • · Purchase of lab-related supplies

    Requirements

    • · Diploma or degree in a biology-related discipline
    • · Experience in bacterial cell cultures
    • · Prior knowledge of molecular biology techniques, such as PCR and cloning is desired
    • · Capacity to work with minimal supervision
    • · Well organized with excellent record keeping skills.
    • · Good command of written and spoken English
    apply now
  • Postdoctoral Associate

    IRG_AMR_2018_012

    LbL Nanoparticle Systems for Biofilm Targeting against Antimicrobial Resistance

    Job description

    The P.T. Hammond research lab at the Singapore-MIT Alliance for Research and Technology Centre, in collaboration with the M.B.E. Chan Lab at Nanyang Technological University, Singapore, will develop electrostatically assembled nanolayered particles for the targeting of infections in biofilms.

    We seek to investigate these systems with the ultimate intent of developing promising systems that can be translated to meaningful clinical applications.

    This position is located at the Singapore-MIT Alliance for Research and Technology Centre at CREATE (1 CREATE Way) within the National University of Singapore campus in Singapore, and is in collaboration with efforts at the Nanyang Technological University.

    Requirements

    • · PhD degree with strong biomaterials background
    • · Experience with polymer synthesis and characterization, cell culture and biological laboratory know-how
    • · Ability to work collaboratively and manage interactions with faculty and a broad range of senior and junior research collaborators
    • · Highly motivated and independent
    • · Good command of written and spoken English
    • · Experience with biological assays, confocal microscopy, or work with bacteria and/or microbiology background is considered favorable but not required
    apply now
  • Postdoctoral Associate

    IRG_AMR_2018_009

    Job description

    The Postdoctoral Associate will lead the bioinformatic analysis of metagenomic sequence data from clinical trials and participate in whole genome analysis. The candidate will develop new approach for understanding environmental surveillance data, including metagenomics and metabolomics data from sewage and river water. The candidate will also prepare and publish scientific manuscripts and develop robust software tools and visualizations.

    Requirements

    • · PhD degree in a biological or related discipline.
    • · Deep knowledge of biological sequence analysis, and familiarity with standard databases.
    • · Python programming proficiency
    • · Experience with molecular biology is desired, especially 16S library construction.
    • · Good command of written and spoken English
    apply now

Technology Platforms

Flow Cytometry

Phenotypic analyses and cell sorting

  • Instrumentation

    1. Attune NxT Analyzer

    • • Cell phenotypic analysis
    • • 4 laser system (R, Y, B, V)

    2. BD FACS Aria II

    • • Bulk & single cell sorting
    • • 4 laser system (R, Y, B, UV)
  • Support

    • • Antibody panel design
    • • Sample preparation and staining
    • • Data acquisition and analysis (FlowJo)
  • Scope

    • • Mammalian cells (cell lines, primary tissue-derived)
    • • Infection models (parasitic, viral and bacterial infection of mammalian cells)
    • • Bacteria

Technology Platforms

Mass Spectrometry

Metabolomics, lipids, epi-omic, proteomics

  • Instrumentation

    Triple Quadrupole LC-MS

    • 1. Agilent QQQ6490
    • 2. Agilent QQQ6460

    Quadrupole Time of Flight LC-MS

    • 3. Agilent QTOF6550
    • 4. Agilent QTOF6520
  • Support

    • • Methods development
    • • Sample preparation
    • • Data acquisition and analysis
  • Scope

    • • Targeted and untargeted metabolomics
    • • Targeted proteomics
    • • Epitranscriptomics: RNA and DNA modifications
    • • Lipid mediator profiling: oxylipins
    • • Accurate mass analysis
    • • Drug metabolism/ pharmacokinetics (DMPK) studies

Technology Platforms

ForteBio Octet

High-throughput real-time measurement of biomolecular interactions

  • Instrumentation

    1. Octet Red96 System

    • • 8 biosensors
    • • Up to 96 samples

    Quadrupole Time of Flight LC-MS

    • 3. Agilent QTOF6550
    • 4. Agilent QTOF6520
  • Support

    • • Methods development
    • • Sample preparation and data acquisition
  • Scope

    • • Label-free detection of biomolecules
    • • Protein quantitation (pg/ ml to mg/ml range)
    • • Affinity characterization
    • • Binding kinetics
    • • High sensitivity ELISA detection

Technology Platforms

Quanterix SR-X

Ultra-sensitive biomarker detection system

  • Instrumentation

    1. QUANTERIX SR-X

  • Support

    • • Multiplex design
    • • Establish / validate new molecule detection
  • Scope

    • • Ultrasensitive multiplex detection of biomolecules
    • • Direct measurement in complex samples (serum, blood, sputum)

Technology Platforms

Quantitative PCR

Real-time and digital drop PCR suites

  • Instrumentation

    • 1. Bio-Rad CFX96 Real-time System (qPCR)

    • 2. Bio-Rad C1000 Thermal cycler (qPCCR)

    • 3. Bio-Rad QX-200 (Digital droplet PCR, ddPCR)

    • 4. Bio-Rad C1000 Thermal cycler (ddPCR)

  • Scope

    • • Relative (qPCR) and Absolute (ddPCR) quantitation of gene expression
    • • Pathogen detection
    • • Viral load quantitation
    • • Expression knockdown quantitation (siRNA / RNAi, MicroRNA)
    • • Rare allele detection (ddPCR)

Technology Platforms

Microscopy and Imaging

Immunohistochemistry and fluorescence-based microscopy

  • Instrumentation

    • 1. Leica Instruments Microtome

    • 2. Zeiss LSM700 Confocal Microscope

    • • 4 laser system (405nm, 488nm, 555nm, 639nm)
    • • z-stack and time-lapse capability
  • Support

    • • Paraffin- and cryo-sectioning
    • • Immunohistochemistry (H&E staining)
    • • Fluorescence panel design and methods development
    • • Image acquisition
  • Scope

    • • Relative (qPCR) and Absolute (ddPCR) quantitation of gene expression
    • • Pathogen detection
    • • Viral load quantitation
    • • Expression knockdown quantitation (siRNA / RNAi, MicroRNA)
    • • Rare allele detection (ddPCR)

Five ways to get involved

We'd love to hear from you.

Terms and Privacy