Combining Raman and SRS imaging to probe drug distribution in mammalian cells

About the Project

This PhD proposal is to develop Raman spectroscopy, optical-photothermal infrared (O-PTIR) and stimulated Raman scattering (SRS) microscopy for measuring drug and xenometabolite distributions in mammalian cells with high spatial and chemical resolution. Raman spectroscopy will provide detailed molecular fingerprints of the drug and cellular components, enabling identification and localization. SRS will enhance imaging speed and sensitivity, allowing real-time, label-free visualization of drug dynamics within live cells. Together, these techniques offer complementary strengths – quantitative chemical specificity from Raman and high-speed imaging from SRS. This integrated approach will reveal drug localization, uptake, intracellular trafficking, as well as drug metabolism and will advance our understanding of drug-cell interactions and informing drug design and therapeutic efficacy.

Training:

• Roy Goodacre (CMR) will supervise the experimental design as well as the data analysis aspects to generate chemical maps related to the distribution of drug and metabolites in cellular and tissue systems.
• Howbeer Muhamadali (CMR) will co supervise the experimental design as well as Raman and SRS for the analysis of mammalian cells exposed to active pharmaceutical ingredients.

Papers:

• Lima, C., Muhamadali, H. & Goodacre, R. (2023) Monitoring phenotype heterogeneity at the single cell level within Bacillus populations producing poly-3-hydroxybutyrate by label-free super-resolution infrared imaging. Analytical Chemistry 95, 17733-17740.
• Al Jedani, S., Lima, C., Smith, C.I., Gunning, P.J., Shaw, R.J., Barrett, S.D., Triantafyllou, A., Risk, J.M., Goodacre, R. & Weightman. P. (2024) An optical photothermal infrared investigation of lymph nodal metastases of oral squamous cell carcinoma. Scientific Reports 14: 16050.

Applications need:

• Cover Letter with a personal statement explaining why you want to do this PhD.
• Cover Letter should include experience in analytical science, biochemistry and or computation.
• Detailed CV
• As the PhD is self-funded: please provide evidence that funding is in place for the full 4 years of the PhD programme.