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Read more about the latest news and developments from our researchers. 

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Published on 25-Sep-2017

Assoc. Prof. Andrew Tan and his team have developed a new gel patch prototype that could speed up the healing of a skin wound while minimising the formation of scars. The team unveiled the patch today as a proof-of-concept.
When fully developed, this healing patch could be a boon for diabetic patients, who suffer from hard-to-heal skin lesions and for patients undergoing surgery.
The new patch is unlike other single-purpose patches in the market, which either reduce the scarring or improve healing, but not both.
The NTU research team recently published their findings in Scientific Reports, which is a peer-reviewed journal under the Nature Publishing Group.
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29 June 201​​7
 
 
The Strength of Weak Affinity Interactions
Sten Ohlson, School of Biological Sciences, Nanyang Technological University, Singapore
 
Weak or transient biological interactions with affinities of Kd > μM, either working alone or in concert, play an important role in sustaining a biological system and we are only recently starting to realize their importance in a range of complex biological networks. Due to the difficulties to see them (“how to see a similar tree in the forest”) and the fact that many non-specific interactions are of a transient nature have made them notoriously hard to study and they have been considered as essentially of no value.
 
In my ISMR award lecture, I will attempt to convince you that weak/transient biological interactions can be measured with a number of techniques including affinity chromatography, capillary affinity electrophoresis, surface plasmon resonance and fluorescence techniques. I will highlight the work we have done through the years in weak affinity chromatography (WAC) where transient binding between a receptor and ligand forms the basis for separation and analysis. Of special importance has been the introduction of weak affinity based HPLC/MS based approaches for applications in drug discovery and clinical diagnostics. Examples will be demonstrated on fragment screening for drug development and steroid analysis in clinical chemistry.
 
Furthermore, the dynamic nature of a transient interactions can be of great value in a number of areas. The development of continuous biosensors have been realized by weak binding between the target analyte and a suitable receptor. Examples will be given on carbohydrate sensing including continuous monitoring of glucose for diabetes control. Maybe the most interesting aspects of the realization of the importance of transient interactions among biomolecules is the challenge of the current paradigm of drug design to find the tightest binder (with affinity typically in the nM range) to a given drug target (“the magic bullet approach”). I postulate that a transient binding drug, if properly designed, can be an alternative successful approach to drug discovery. Of special importance is the hypothesis that the success of polypharmacologic drugs (“the magic shotgun approach”) is dependent on the design of weaker binders. I will discuss this in more in detail in my presentation and give some highlights of our work on developing transient polybinders to cancer targets and as antibiotic agents.
 
Even though it is challenging to study weak interactions, tools are now available in affinity technology to study these subtle molecular events. I am convinced that if you suspect of having weak binding events in your research, it can be properly studied and explored favourably.
 


04 April 2017

2016 Winner: Viswanadh Madugula
Michael Way (Editor-in-Chief)

We are pleased to announce that the winner of the 2016 JCS prize is Viswanadh Madugula for his paper entitled ‘The ciliary membrane targeting by a ternary complex comprising transportin 1, Rab8 and the ciliary targeting signal’ (Madugula and Lu, 2016).

The prize, $1000, is awarded annually to a junior researcher who is the first author of the paper that is judged by the Editors and Editorial Board to be the best eligible paper published in Journal of Cell Science that year. To be considered for the prize, the first author must be a student or a postdoc of no more than five years’ standing.

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01 December 2016

A/Prof Gao Yong-Gui and his research team in collaboration with Asst. Prof Oliver Mueller-Cajar as well as involving A/Prof Newman Sze uncover structural insights into the LCIB protein family revealing a new group of β-carbonic anhydrases

Many aquatic microorganisms have evolved CO2-concentration mechanisms (CCMs) to boost photosynthesis. The green algae Chlamydomonas reinhardtii has the best-characterized eukaryotic CCM model. Mutants lacking the limiting CO2-inducible B protein (LCIB) protein are unable to survive in air. To investigate the molecular underpinnings of this effect, researchers biochemically and structurally characterized a number of LCIB homologues from diverse organisms, including constitutively carbonic anhydrase (CA)-active proteins. The research discovered that LCIB proteins structurally resemble β-CAs in both overall fold and active site architecture. The results provide insight into the molecular mechanism of the LCIB family involved in microalgal CCMs.

Paper is published on PNAS (Proceedings of the National Academy of Sciences of the United States) online on 01 December 2016.

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24 October 201​​6
Assoc. Prof. Liang Zhao-Xun and his team in collaboration with Asst. Prof. Yang Liang and his researchers uncover how blocking bacterial protein may combat drug-resistant biofilms. This research makes it to the cover feature of Science Signaling.  
   
The bacterial messenger cyclic diguanylate monophosphate (c-di-GMP) binds to various effectors, the most common of which are single-domain PilZ proteins. These c-di-GMP effectors control various cellular functions and multicellular behaviors at the transcriptional or posttranslational level. We found that MapZ (methyltransferase-associated PilZ; formerly known as PA4608), a single-domain PilZ protein from the opportunistic pathogen Pseudomonas aeruginosa, directly interacted with the methyltransferase CheR1 and that this interaction was enhanced by c-di-GMP. In vitro assays indicated that, in the presence of c-di-GMP, MapZ inhibited CheR1 from methylating the chemoreceptor PctA, which would be expected to increase its affinity for chemoattractants and promote chemotaxis. MapZ localized to the poles of P. aeruginosa cells, where the flagellarmotor and other chemotactic proteins, including PctAandCheR1, are also located. P. aeruginosa cells exhibit a random walk behavior by frequently switching the direction of flagellar rotation in a uniform solution. We showed that binding of c-di-GMPtoMapZ decreased the frequency of flagellar motor switching and that MapZ was essential for generating the heterogeneous motility typical of P. aeruginosa cell populations and for efficient surface attachment during biofilm formation. Collectively, the studies revealed that c-di-GMP affects flagellar motor output by regulating the methylation of chemoreceptors through a single-domain PilZ adaptor protein.
 
​This research article has been published on Science Signaling Volume 9, Issue 450, 18 October 2016.
 


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18 June 201​​6

Nanyang Assoc. Prof. Gao Yonggui and his team’s research on the structure of the GTP form of elongation factor 4 (EF4) bound to ribosome makes it to the front cover feature of the Journal of Biological Chemistry. 

Three ribosome-dependent translational GTPase (trGTPase) factors EF-G, EF4, and BipA share structural similarity but have distinct functions. For instance, EF-G is well known for catalyzing the translocation of the mRNA-tRNAs along the ribosome.  As for EF4, it is still unclear with which state of the translating ribosome EF4 interacts with and what happens next, despite it being highly conserved in bacterial, mitochondrial, and chloroplast genomes.

We present the structure of the GTP form of EF4 bound to the ribosome with P- and E-site tRNAs. Interestingly, in contrast to the clockwise rotation previously observed in the presence of EF4-GDP, our structures reveal both unrotated and counter-clockwise rotated states of the ribosome. Our findings shed light on the interactions formed between EF4, the ribosome, and P-site tRNA as well as illuminating the GTPase activation mechanism, as well as offers the structural basis for EF4 functioning in protein synthesis.   

 

​This research article has been published on JBC Volume 291, No. 25, Issue 17 June 2016.

 

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18 April 201​​6

Nanyang Asst. Prof. Yansong Miao and research team uncover a mechanism of how cell cycle regulate actin filament by modulating the phosphorylation of actin cross linking protein fibrin.

This work has been done in collaboration with Assoc. Prof. Yuguang Mu and Professor David Drubin (University of California, Berkeley). Actin network formation require collaborative efforts from multiple actin binding proteins. Actin filaments receive upstream signals during physiology and pathological conditions in eukaryotic cells, which is challenging to study how actin network are regulated directly. Many of actin binding protein contains intrinsic disorder region (IDR), which is flexible for multiple purposes, such as protein-protein interaction. Dr. Miao found cell cycle regulate actin binding protein fimbrin via phosphorylation on IDR by Cdk1, which causes the conformational change and regulate it’s interaction with actin filament. This fundamental research in phospho-regulation of actin binding protein will inspire some future research on how physiological and pathological signals regulate actin filament and the corresponding biological processes. 

This research article has been published online in Nature Communications 7, Article number: 11265, on 12 April 2016. 

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30 March 201​​6

Interdisciplinary research between Asst. Prof Yang Liang, Assoc. Prof Newman Sze Siu Kwan and Prof Michael Givskov, discover way to improve effectiveness of antibiotics 

NTU Scientists have discovered that antibiotics can continue to be effective if bacteria’s cell-to-cell communication and ability to latch on to each other are disrupted.

 

This research breakthrough is a major step forward in tackling the growing concern of antibiotic resistance, opening up new treatment options for doctors to help patients fight against chronic and persistent bacterial infections.

The research paper has been published in Nature Communications 7, Article number: 10750, published on 19 February 2016​.

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9 March 201​​6

Asst. Prof Lu Lei and team have found a novel imaging-based method to quantitatively localize Golgi proteins at nanometer resolution. The method reveals different intra-Golgi trafficking of secretory cargoes.

Cellular functions of the Golgi are determined by the unique distribution of its resident proteins. Currently, electron microscopy is required for the localization of a Golgi protein at the sub-Golgi level. Asst. Prof Lu Lei and team developed a quantitative sub-Golgi localization method based on centers of fluorescence masses of nocodazole-induced Golgi ministacks under conventional optical microscopy. The method is rapid, convenient, and quantitative, and it yields a practical localization resolution of 30 nm.
 
The research paper has been published in the 1 March 2016 Issue of Molecular Biology of the Cell.

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13 January 2016

Prof Yoon Ho Sup and research team uncover a novel structural basis of nucleic acid recognition by immunophilin

Immunophilins are a versatile family of chaperone proteins that control cis-trans isomerization of peptidylprolyl bonds in proteins and also serve as molecular receptors for several immunosuppressive drugs such FK506, cycloporin, and rapamycin. Most FKBPs are distributed in the cytoplasm. Interestingly, FKBP25 was the first FKBP family member that was identified to mainly reside in the nucleus and interacts with chromatin-related proteins and transcription factors, and thus is suggested to interact with nucleic acids. Currently the structural basis of nucleic acid binding by FKBP25 is unknown. Prof Yoon’s team has determined nuclear magnetic resonance (NMR) solution structure of the full-length human FKBP25 and studied its interaction with DNA. The FKBP25–DNA complex provides a novel structural model of immunophilin-mediated nucleic acid recognition.

The research paper has been published on Nucleic Acids Research online on 13 Jan 2016.

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17 December 2015

Man-made functional proteins are ‘holy-grail’ in Structural Biology

Assoc Prof. Surajit and his team reported the design of four and six-stranded β-sheet peptides that demonstrated high affinity binding to heme and perform heme-protein functions such as peroxidase activity and electron-transfer in membrane. This research contributes towards the development of a novel class of de novo designed heme and metallo-proteins.

Paper has been published online in Chemical Science, a journal of the Royal Society of Chemistry on 17 December 2015

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8 September 2015

Dr Sugrue’s laboratory at the School of Biological Sciences and collaborators from NUHS and DSO National Laboratories have provided the first detail characterisation of respiratory syncytial virus (RSV) morphogenesis in the human nasal epithelium.

RSV infection is a leading cause of viral pneumonia in young children. The nasopharyngeal cavity is a primary route of RSV infection in humans, and using stem cell technology they were able to examine RSV-infected human nasal epithelium in a tissue culture dish. They showed that RSV infection specifically occurs in the ciliated epithelial cells within the nasal epithelium, and that virus infection induced changes in the cilia axoneme that resulted in extensive cilia dysfunction. The RSV-induced cilia dysfunction that is described may provide a mechanism that facilitates the transmission of RSV within the upper respiratory tract. Furthermore, this virus-induced change in the nasal epithelium may also be a factor in the colonization of the respiratory tract by opportunistic respiratory pathogens following RSV infection.

The paper has been highlighted in the journal Virology, Issue 484, 395-411 published on 28 July 2015.

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4 September 2015

Team of SBS immunology lab- Sheng Jianpeng, Christiane Ruedl and Klaus Karjalainen- has found that most tissue-resident macrophages orginate from fetal hematopoietic stem cells rather than yolk sac as suggested previously.

This work suggests that although most tissue-resident macrophages are born from fetal precursors and then maintained in situ for the rest of mouse life, they are not derived from yolk sac like brain microglia but from classical fetal hematopoietic stem cells.

The research paper has been published on Immunity, Volume 43, Issue 2 (Page 382-393) on 18 August 2015. This work was supported by MOE Tier 1 grant, RG49/13.

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31 August 2015

Latest research of Assoc. Prof Christiane Ruedl and her team identified a new pathway how to control intestinal inflammation

Assoc. Prof Christiane Ruedl and her team have discovered the importance of a distinct intestinal dendritic cell subset in controlling gut inflammation. This discovery contributes in advancing our understanding of inflammatory bowel diseases and opens new opportunities for therapeutical interventions.

The research paper has been published on Nature’s Mucosal Immunology online on 15 July 2015.

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25 August 2015

Associate Prof Gao Yong-Gui and research team uncover mechanical insights into translational regulation by BipA

BipA (BPI-inducible protein A) gene is highly conserved among bacterial and chloroplast genomes and has been implicated in regulating a variety of cellular processes including bacterial virulence, symbiosis, various stress responses, resistance to host defenses, swarming motility, biofilm, and capsule formation. BipA is an essential factor for bacterial survival at low temperature, nutrient depletion, and various other stress conditions. First, we determined the crystal structures of isolated BipA in various biologically states (nucleotide bound/free). Furthermore, in collaboration with Asst. Prof. Shashi’s lab, we also determined the structure of BipA as a translational GTPase bound to the ribosome in its active form, using the newly established Cryo-EM facility in NTU. Because no other stress response factor is known to interact with the A-site tRNA in ribosome, our results provide a novel mechanistic insight of translational regulation by BipA. In particular, the structure of BipA bound to ribosome with A- and P-site tRNAs reveals a new intermediate state, which implies a function for BipA in positioning of A-site tRNA or in preventing translocation by EF-G, in response to stress. Our findings also boost ribosome as one of the richest validated targets for antibacterial drug discovery.

Paper is published on PNAS (Proceedings of the National Academy of Sciences of the United States) online on 17 August 2015.

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31 July 2015

Dr Stephan Schuster and his team together with US scientists has mapped the complete genome of the woolly mammoth.

This new research development could help resurrect the extinct woolly mammoth in future. Work by the research teams on the long-extinct woolly mammoth is opening the door to resurrecting this ice age creature from the dead. The team has produced, for the first time, a high-resolution genome or genetic blueprint of the giant mammal. This is the first of many steps which would make it possible to bring it to life, said NTU’s Dr Stephan Schuster, who is part of the Singapore-United States team involved in the effort.

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30 June 2015

Multidisciplinary collaborative research between Prof Yoon Ho Sup, SBS/NTU and Prof Kwang-Soo Kim, McLean Hospital/Harvard Medical School find a new way to treat Parkinson’s Disease (PD).

Orphan nuclear receptor Nurr1, a promising target for PD, is thought to be a ligand-independent transcription factor. So far, no small molecule has been identified that can bind to its ligand binding domain. Teams identified Nurr1 agonists among FDA-approved drugs, sharing an identical chemical scaffold. Remarkably, these compounds (chloroquine and amodiaquine), which are used as antimalarial drugs, not only directly bind to Nurr1 but also ameliorate behavioral defects in a rodent model of PD.

Parkinson’s disease (PD), is the most prevalent movement disorder with no available treatments that can stop or slow down the disease progress. This study shows that Nurr1 could serve as a valid drug target for neuroprotective therapeutics of PD. The work has been published in PNAS (Proceedings of the National Academy of Sciences of the United States of America) online on 29 June 2015.

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29 April 2015

Prof Su I-hsin and team uncovers a new function for Ezh2 and is featured as cover story in Nature Immunology.

Ezh2 is an important epigenetic regulator that modulates chromatin structure and gene expression. Asst Prof I-hsin Su & colleagues identify a cytoplasmic role for Ezh2 whereby it controls extravasation of innate leukocytes through talin methylation and thereby influences inflammatory responses in vivo. This research article has been accepted and featured as a cover story in Nature Immunology (Volume 16, Pages: 505-516 (2015))

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22 April 2015

Prof Grüber research team’s paper makes it to ‘Cover Page & Feature Article’ in the Journal of Molecular Biology.

Prof Grüber Gerhard and his team of researchers’ paper ‘The Molecular Motor F-ATP Synthase Is Targeted by the Tumoricidal Protein HAMLET’ is featured and highlighted in the notable Journal of Molecular Biology, Volume 427, Issue 10. Their featured paper was also given a commentary write up by an expert in the field, Prof Egbert Boekema from Netherlands, ‘A Passive Function of Mitochondrial ATP Synthase: Target for Tumor Killer HAMLET’.

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6 April 2015

SBS Scientists discover a new way to treat dementia and improve patient’s memory

Dr. Lee Wei Lim & Asst Prof Ajay Vyas’s team have discovered a new treatment for dementia, by sending electrical impulses to specific areas of the brain to enhance the growth of new brain cells.

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11 February 2015

Prof. Andrew Tan’s research team develops an antibody to speed up recovery for influenza and pneumonia patients

This patent-pending antibody has generated much interest globally, with two MNCs winning the rights to license the antibody for research in vaccine and drug development. Currently the team is developing a diagnostic kit which can help doctors track the recovery progress of flu and pneumonia patients.

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9 February 2015

Prof. Gruber’s research team selected for ‘Paper of the Week!’ on US’s Journal of Biological Chemistry

Awarded to only the top 2% of papers with overall importance, Prof. Gruber and his team’s paper titled - “Crystal Structure of Subunits D and F in Complex Gives Insight into Energy Transmission of the Eukaryotic V-ATPase from Saccharomyces cerevisiae” was selected “Paper of the Week” in the US’s notable Journal of Biological Chemistry (JBC).

Research Significance

First crystallographic structure of eukaryotic V-ATPase subunit D and entire subunit F is presented which gives a mechanistic understanding of the subunit DF assembly and its key roles in enzyme catalysis and regulation

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16 January 2015

Front Cover Feature of A/Prof. Gao Yonggui research in January 2015 issue of Chemical Science Journal.

A/Prof. Gao Yonggui and his team paper titled, “A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor of N6-methyladenosine demethylase FTO” was selected as a front cover freature on 2015 January’s issue of Chemical Science Journal.

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12 December 2014

Latest research lead by A/Prof. Zbynek Bozdech discovers reasons for Malaria's Drug Resistance.

Scientists from Nanyang Technological University (NTU) have discovered exactly how the malaria parasite is developing resistance towards the most important front-line drugs used to treat the disease.

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