PhD Research Projects

At IDMxS, we explore interdisciplinary research in molecular analytics, optical and electrochemical sensor technology, data sciences, interfacial chemistry, and more. Below is a list of available projects for our PhD programme; please note that this list might not include all available projects, so we recommend checking with individual principal investigators for further opportunities.

Projects:

Synthesis and Characterization of Conjugated Oligoelectrolytes for Bio-imaging Applications
Synthesis of Novel Conjugated Oligoelectrolytes for Combatting Antimicrobial Resistance
Information and decision theory in biosensing and diagnostics

Synthesis and Characterization of Conjugated Oligoelectrolytes for Bio-imaging Applications

Supervisor: Prof Guillermo Bazan

Fluorescent reporters are the basis of powerful techniques that visualize and quantify biological processes, embodying an essential facet of chemical biology. Driven by merits of non-invasiveness, high spatial and temporal resolution, high sensitivity, real-time and in situ detection, fluorescence technologies serve to reveal the location and detect intracellular molecules, even at the single-molecule level.[1-2]

Conjugated oligoelectrolytes (COEs) are a class of fluorescent small molecules with a hydrophobic light-harvesting π-conjugated backbone and charged pendant ionic side chains. The ionic groups confer solubility in aqueous media and specific interactions with charged targets through electrostatic interactions. The affinity of linear cationic COEs towards negatively charged biological phospholipid bilayers has enabled diverse applications including biosensors, transmembrane transport, bioelectrochemical systems, and electron-transfer agents, see Figure 1.[3-4] Furthermore, the emissive nature and modular designability from simple subunits make COEs a promising molecular platform for designing bioimaging platforms.[5]

Our goal is to design and synthesize novel COE molecules with unique responsive properties and include them in emerging single molecule detection techniques. Particularly relevant is fluorescence lifetime imaging microscopy (FLIM) to identify biomarkers for aging and bacteria that are resistant to antibiotics.

Figure 1. (a) Structures of COE-S6 and phospholipid bilayers; (b) scheme of COE molecular applications.

References

  1. Kircher, M. F.; Gambhir, S. S.; Grimm, J., Noninvasive Cell-tracking Methods. Nat. Rev. Clin. Oncol. 2011, 8 (11), 677-688.
  2. Lee, S. K.; Mortensen, L. J.; Lin, C. P.; Tung, C.-H., An Authentic Imaging Probe to Track Cell Fate From Beginning to End. Nat. Comm. 2014, 5 (1), 5216.
  3. Wang, B.; Queenan, B. N.; Wang, S.; Nilsson, K. P. R.; Bazan, G. C., Precisely Defined Conjugated Oligoelectrolytes for Biosensing and Therapeutics. Adv. Mater. 2019, 31 (22), 1806701.
  4. Kirchhofer, N. D.; Rengert, Z. D.; Dahlquist, F. W.; Nguyen, T.-Q.; Bazan, G. C., A Ferrocene-Based Conjugated Oligoelectrolyte Catalyzes Bacterial Electrode Respiration. Chem 2017, 2 (2), 240-257.
  5. Zhou, C.; Cox-Vázquez, S. J.; Chia, G. W. N.; Vázquez, R. J.; Lai, H. Y.; Chan, S. J. W.; Limwongyut, J.; Bazan, G. C, Water-soluble extracellular vesicle probes based on conjugated oligoelectrolytes Sci. Adv. 2023, 9, eade2996

For more information, please contact: Prof Guillermo Bazan (guillermo.bazan@ntu.edu.sg)

Synthesis of Novel Conjugated Oligoelectrolytes for Combatting Antimicrobial Resistance

Supervisor: Prof Guillermo Bazan

The antimicrobial resistance (AMR) crisis is one of the key health challenges of the 21st century and a major public health threat. Predictions by the UN show that at the current trajectory, up to 10 million deaths annually will be attributable to AMR. Despite this, there has been a lack of interest in the problem owing to inherent challenges of drug development and poor economic viability. There thus remains a need to develop fundamentally new antimicrobial agents and to facilitate further development.

Conjugated oligoelectrolytes are a class of molecules originally designed to interface with biological membranes, allowing for rational fine-tuning of biophysical properties to affect transmembrane electron transfer and biological fitness.[1] Structure-Activity Relationships (SARs) have elucidated strategies to balance antimicrobial efficacy, cytotoxicity, and in vivo tolerability.[2] Owing to the novel modular molecular scaffold dissimilar to current commercial antibiotics, COEs feature a distinct mechanism of action and low propensity for bacteria to develop resistance. These features make them well placed to develop novel lead compounds for targeted antimicrobial applications. Indeed, a recent publication from our group highlights the therapeutic potential of this new class of drugs, particularly against difficult to treat lung infections .[3,4]

Figure 1.  A specific COE, namely COE-PNH2, proved successful against non-tuberculous mycobacteria mouse infection models. Drugs that can disrupt the structure and composition of the mycobacterial envelope is crucial for new treatment strategies and combating antimicrobial resistance.

References

  1. H. Yan et al., Chem. Sci., 2016, 7, 5714-5722.
  2. J. Limwongyut et. al., Chem. Sci., 2020, 11, 8138-8144.
  3. https://news.nus.edu.sg/breakthrough-antibiotic-against-mycobacterial-infections/
  4. K. Zhang et al., Science Translational Medicine, 2024, 16, Article 735.

For more information, please contact: Prof Guillermo Bazan (guillermo.bazan@ntu.edu.sg)

Information and decision theory in biosensing and diagnostics

Supervisor: Asst Prof Matthew Foreman

Digital molecular assays aim to detect, identify, and quantify different molecular species in a massively parallel manner. They therefore rely on the ability to execute potentially millions of single molecule assays, each of which can be read out individually. Optical imaging offers a natural, fast and inherently digitised readout whereby ultimately each individual pixel could correspond to readout of different molecular assays. Imaging quality is often of secondary importance in digital molecular analytics, where the task focuses more on binary detection, identification of individual molecular species or disease diagnosis. In such scenarios an informatic approach, whereby an imaging assay is considered as a channel through which information is transmitted and extracted computationally, is more appropriate. This project will analyse different optical assays and detection protocols from an information standpoint. Information of disease progression and biological function obtained from different assay types will be quantified and the advantages of the digital detection paradigm investigated. This project will also draw ideas from estimation, classification and detection theory and apply them in the digital assay and computational imaging paradigm. As such algorithms will be developed for estimation of key assay parameters e.g. pathogen concentration, and critically, assessment of the reliability of resulting diagnostics. Through this approach the project aims to develop diagnostic tools with enhanced sensitivity.

The ideal candidate has an enthusiasm for informatics, mathematics, statistical analysis and algorithm development. They would have a first degree in physics, mathematics or engineering with strong analytical, mathematical and programming skills. We consider an applicant’s Grade Point Average (GPA) an important factor in assessing their suitability.

About the GroupOptical Theory Group

We are a theoretical research group at the School of Electrical and Electronic Engineering and the Institute for Digital Molecular Analytics and Science at Nanyang Technological University, Singapore. The group is lead by Assistant Professor Matthew R. Foreman (PhD, MPhys). We have a strong background in physics, mathematics and optical modelling.

Our research focuses on optical and plasmonic sensing, polarisation sensitive imaging, disordered media and electromagnetic theory. We seek to drive progress in quantitative bioimaging and sensing, through development of novel modalities, system modelling and optimisation, and fundamental physical insights.

For more information, please contact: Asst Prof Matthew Foreman (matthew.foreman@ntu.edu.sg)

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