1st year u/g students, 2nd year u/g students, 3rd year u/g students
Student Responsibilty with support from IIP and/or Host Organization
International Internship Program
About: The University of Strathclyde is a leading international technological University located in the heart of Glasgow. Their University is one of the UK’s top 20 research universities. The Department of Pure and Applied Chemistry was ranked 4th in the UK with 94% of its research rated as internationally excellent or internationally leading. They have one of the largest research schools in the UK, with expertise ranging from analytical chemistry to materials science, and from biological chemistry to organic and inorganic synthesis; and national and international collaborations are in place in all research areas.
Intern Responsibilities: IIP interns will work on one or more of the following projects:
Using Raman Spectroscopy as a Tool in the Fight to Cure Cancer- Unlike other cellular biomolecules, which are readily imaged using fluorescent labels, lipids are notoriously difficult to image effectively in cells. Recently we have developed new methods to image cellular lipid distribution using Raman spectroscopy in live cancer cells. This provides a vital tool, which we are using to address key areas in cancer biology. Metabolic aspects of cancer, such as lipid synthesis, have become significant targets for cancer therapy. Lipid synthesis is upregulated in cancer, and therefore, drugs that inhibit lipid synthesis have proven effective in targeting cancer cells. This project will involve learning a wide variety of practical skills from cell culture to Raman spectroscopy. You will image lipids in cancer cells using Raman spectroscopy and investigate how drugs targeting different aspects of lipid synthesis effect the lipid composition of these cells. You will also get the opportunity to learn about data processing and analysis techniques, with the option to develop new methods for extracting important information on lipid composition from the spectral data collected. Additionally we will investigate the use of labeled metabolites, which we will feed to cells and track using Raman spectroscopy, to give us new insight into lipid metabolism in cancer cells and selecting effective drugs for treatment. This is a very new area of research and this project offers great potential for generating results for publication.
Scaffold Hopping Approaches to Novel Autotaxin Inhibitors- Autotaxin (ATX) is a ubiquitous ectoenzyme that hydrolyzes lysophosphatidylcholine (LPC) to form the bioactive lipid mediator lysophosphatidic acid (LPA). LPA activates specific G-protein coupled receptors to elicit downstream effects leading to cellular motility, survival, and invasion. Through these pathways, upregulation of ATX is linked to a number of proliferative diseases, including idiopathic pulmonary fibrosis.In their laboratories, we have developed a novel class of inhibitors, using a scaffold hopping approach based on the literature analogue PF-8380. This project will centre around the design, synthesis and biological testing of a new scaffolds designed as isosteric replacements of the PF-8380 piperazine core.
Bioinspired Nanopores- This experimental project in (bio)materials science/chemistry will develop nanopores inspired by the nuclear pore complex (NPC) for controlling protein transport. NPCs are ~50 nm wide pores located on the nuclear envelop of all eukaryotic cells. They are the sole conduits for selecting specific proteins and polynucleotides for passage between the cell nucleus and the cytoplasm, while rejecting all the biomacromolecular species existing in the cellular milieu. NPC mimics will enable selective nanopores that have wide potential such as in the production of protein-based drugs and enzymes, in sensing of biomarkers, and encapsulating drugs for targeted delivery. To mimic NPCs, the research is studying how NPC function relies on the polymer-like, unfolded polypeptide chains observed to cover the inner pore surface of the pores. We will compare the feasibility of the two main hypotheses of NPC function—the polymer brush “virtual gating” model and the polymer hydrogel “selective phase” model. The student will work with the group to graft a model polymer structure onto a synthetic nanoporous membrane scaffold. The passage (diffusion) of proteins will be measured by a nanoporous waveguide optical technique. This is a challenging project requiring commitment and intellectual creativity. The student will have a chance to learn various techniques in surface chemistry, polymer science, and materials engineering. Depending on interest, the student’s research will focus on selected aspects of surface chemical functionalization, polymer grafting, protein assays, and/or surface measurement (e.g. waveguide sensing, SPR, ellipsometry, atomic force microscopy, electron microscopy, water contact angle, etc.).
Novel Iridium-Based Catalysts for Hydrogen Isotope Exchange and Reduction Processes- Transition metal-mediated hydrogen isotope exchange (HIE) is a technique of increasing importance, with a range of applications spanning all aspects of organic synthesis (1→2, Scheme 1). Importantly for medicinal chemists, such direct and flexible labelling processes now represent a central tool for the fast and efficient incorporation of a tracer into drug candidates, enabling various metabolic, stability, and toxicity studies to be performed earlier in the drug design process. Recent studies from their own laboratory have disclosed a series of highly active iridium(I) catalysts of the type 3, capable of delivering heavy isotopes of hydrogen (deuterium and tritium) to aromatic molecules via an ortho-directed C-H insertion process. This suite of catalysts 3 consistently outperforms previous benchmark catalysts across a broad range of substrates, and, indeed, are able to label substrates, at low catalyst loading, where other Ir complexes fail completely even at stoichiometric levels. To date, we have shown that their catalysts are capable of efficiently mediating a range of labelling and reduction processes (Scheme 2). Labelling of aromatic systems is directed by a broad range of functional groups, including ketones, amides, esters, nitroarenes, and an array of N-heterocycles, all with high levels of D-incorporation under mild conditions. They have recently extended this work to include the labelling of non-aromatic unsaturated systems, and to the highly challenging aromatic primary sulfonamides. Catalysts 3 can also mediate the reduction of carbon-carbon double and triple bonds, with highly substituted alkenes being reduced in excellent yield, and tuneable conditions to reduce alkynes to either alkanes or (Z)-alkenes. In this project, the IIP intern will augment their range of catalysts 3 with novel NHC/phosphine-Ir complexes. The design of these complexes will be based on the demands of new, challenging substrates for the labelling and reduction processes in addition to other emerging applications for this family of catalysts in organic synthesis. As part of this programme, the IIP intern will gain experience of both organometallic chemistry and organic synthesis through the preparation of the iridium complexes and a spectrum of organic substrates, as well as via the central catalyzed labelling and reduction experiments, and post-labelling manipulations.
Calculating physico-chemical properties of bioactive molecules from molecular theories of solvation- Experimental assays of physico-chemical properties (solubility, pKa, octanol-water partition coefficient, etc) are used in the pharmaceutical industry to identify candidate drug molecules that might be administered by the preferred oral route. However, such experiments are expensive, time-consuming and can only be applied to molecules that have already been synthesized. An alternative approach is to use computer simulations to calculate the properties of putative drug molecules prior to their synthesis. In collaboration with scientists at AstraZeneca in Sweden, they have recently developed several methods for predicting solvation thermodynamics parameters of bioactive molecules in view of potential applications in industry. One such method is based on a molecular theory of solutions, the Reference Interaction Site Model (RISM). The IIP intern will have the opportunity to be involved in large-scale computational screening of thermodynamic properties of drug-like molecules by these new methods. The project will provide research training in physical chemistry (including statistical mechanics and thermodynamics) and modern computational chemistry techniques (including molecular dynamics simulations and molecular integral equation theory).
Qualifications: IIP candidates must have a strong background in chemistry and interests in lab work. Skills in all the standard manipulations carried out in the chemistry laboratory, i.e. titration, distillation, measurement, etc. are highly recommended.