PhD Research Project
Titled: Fundamentals of Tandem Mass Spectrometry and Multimodal Fragmentation of Lipids and Polymers
Supervised by Professor Peter B. O'Connor (Department of Chemistry)
Project 1: Analysis of Glycerophospholipid (GPEtn) Complex using CAD/CID, EID, and IRMPD, Fourier-Transform Ion Cyclotron Resonance Mass Spectrometry
Supervised by Professor Peter B. O'Connor (Department of Chemistry)
Comprehensive structural characterisation of complex lipids, such as Glycerophospholipids (GPEs) by tandem mass spectrometry (MS/MS) continues to present a considerable challenge. Although there have been a number of studies which have used high-resolution mass spectrometry with various fragmentation methods, detailed structural and spatial distribution of these complex lipids still remains relatively unknown. Isomeric and isobaric species have also created immense difficulty in the elucidation and identification of these lipid components, and conventional dissociation methods do not generate fragmentation that permit the isomeric discrimination relative to the position of the double bonds on the acyl chains and the branching points on the glycerol backbone. In this investigation, direct infusion by nano-electrospray ionisation tandem-in-time MS/MS with collisionally-activated/induced dissociation (CAD/CID), electron induced dissociation (EID) and infrared multiphoton dissociation (IRMPD) were used for the detailed structural characterisation of L-α-Phosphatidylethanolamine, dioleoyl (GPEtn). This method enabled site-specific localisation of the double bonds on the acyl chains to be determined and provided sn-positional information of the di-acyl branching point on the glycerol backbone.
Project 2: Combining Quantum Mechanics-Based Calculations and Experimental Solution-State 1D-TOCSY NMR Spectroscopy for the Identification and Simulation of Magnetization Transfer Between (J)-Coupled Spin Systems in Anomeric D-(+)-Glucose
Supervised By Professor Steven P. Brown (Department of Physics)
Solution-state proton nuclear magnetic resonance spectroscopy (NMR) is a highly sensitive method used for the elucidation of various organic complexes, such as D-(+)-Glucose which undergoes anomerisation in solution. However, spectral overlapping from multiple proton (1H) resonances in 1D NMR continues to present a considerable challenge when analyzing such complex mixtures, making it difficult to accurately assign the chemical shifts (δ/ppm) and J-couplings (2J and 3JH-H) values to the associated spins. In this investigation a 1D-selective total correlation spectroscopy (sel-TOCSY) with a single Gaussian (π) pulse and decoupling in the presence of scalar interactions (DIPSI-2) mixing sequence was used in conjunction with 1D 1H-NMR, 2D-hetero nuclear single quantum coherence spectroscopy (HSQC) (13C-1H) and 2D-correlation spectroscopy (COSY) (1H-1H) to determine the molecular connectivities and enable a complete assignment of the overlapped proton resonances within α- and β-D-(+)-Glucose. Implementation of DIPSI-2 ‘spin-lock’ further provided an indication of the experimental cross-peak (I2z) intensities and magnetization transfer within the D-(+)-Glucose spin-network relative to the TOCSY mixing time (τmix) between 10-100 ms. The experimental pulse sequence, internal Hamiltonian and spin system parameters were then compiled using a scripting interface (tcl), where the cross-peak intensities were simulated using a simulation package for solid-state NMR spectroscopy (SIMPSON), that works on the exploitation of the matrix-matrix multiplications and the numerical integration of the Liouville-von- Neumann equation, providing a comparable understanding of the magnetization transfer efficiency between J-coupled spins within α- and β-D-(+)-Glucose.
SIMPSON 1D-TOCSY Code Available at Link opens in a new window
MAS-CDT MSc Mini-Project Groups
Project 1: FT-ICR MS Group (Department of Chemistry)
Project 2: Solid-State NMR Group (Department of Physics)
PhD in Molecular Analytical Science – University of Warwick (2020-Current)
MSc in Molecular Analytical Science - University of Warwick (2018-2020)
MSc (Distinction) in Analytical Science - University of Bradford (2015-2017)
BSc (Hons) (2.i) in Environmental Science with Chemistry - University of Bradford (2010-2014)
Previous BSc and MSc Projects
University of Bradford MSc Dissertation: Interactions of Organic Molecules and Ceramic Clays: Method Development for the Utilisation of Direct Insertion Probe-Mass Spectrometry and Dispersive Confocal Raman Spectroscopy
University of Bradford BSc Dissertation: Determination of Polycyclic Aromatic Hydrocarbons (PAHs) in Top Soil by means of Gas Chromatography-Mass Spectrometry
Professional Experience and Background
Student Chemist- Light Isotope Laboratory, University of Bradford, Department of Archeological and Environmental Science, United Kingdom, 2014.
Student Biomedical Laboratory Technician- University of Leeds, School of Biomedical Science, United Kingdom, 2005.
Conferences and Courses Attended
BMSS (41 Conference) - (Flash Oral Presentation)- Sheffield Hallam University - 8th-9th September 2021.
Title: Multimodal Fragmentation and Two-Dimensional Mass Spectrometry Characterisation of Human Placental Lipid Extracts
Basim R. Hussain1, Edyta Carrion Paczkowska2, Bryan P. Marzullo1, Johanna Paris1, Roberto Angelini2, Mark P. Barrow1, Cathy Thornton2 and Peter B. O’Connor1.
1University of Warwick, Department of Chemistry, Coventry, United Kingdom. 2Swansea University, Medical School, Institute of Life Science, Swansea, United Kingdom
Summary: Lipids are a highly abundant complex class of biomolecules which serve as principal components of mammalian cellular membranes. Lipids provide cell adhesion, energy storage, migration, signal transduction, cellular apoptosis, and gene expression. However, the biophysical architecture of various lipids can provide an insight into the dissociation mechanism in adverse obstetrics, where the lipid pathophysiology can have tremendous implications on a developing foetus, and consequentially on a new-born and the mother. The aim of this study was to develop a dual nano-electrospray ionisation (nESI) 1- and 2-dimensional tandem mass spectrometry method, with collisionally-activated/induced dissociation (CAD/CID), Infrared-multiphoton absorption dissociation (IRMPD) and electron-induced dissociation (EID) fragmentation. This was done to accurately identify the structural characteristic lipidomic signatures in relation to the polar head groups, sn-positional fatty acyl chain lengths and double-bond position, in response to diabetes, obesity, and pro-inflammatory mediators in the patient Human placental tissue matrix.
AS & MAS-CDT Annual Conference (Flash Presentation) - July, 2020.
ASMS (Reboot) (68th Conference) - June, 2020.
EU FT-ICR MS (4th Short Course) - University of Warwick, August, 2019.
MAS-CDT Annual Conference (Flash and Poster Presentation) - Somerset, United Kingdom, July, 2019.
Member of the British Mass Spectrometry Society (BMSS)
Member of the American Society for Mass Spectrometry (ASMS)
Member of the Royal Society of Chemistry (RSC)
Engineering and Physical Sciences Research Council (EPSRC) Scholarship for Integrated MSc and PhD in Molecular Analytical Science, University of Warwick - September, 2018.
Photography- Primarily scientific, fine art and architectural photography.
Reading- Material relating to science fiction, cultural and comparative history, geopolitics and south-east Asian philosophy.
Basim R. Hussain
MAS-CDT and FT-ICR MS Group
Ion Cyclotron Resonance Laboratory
Department of Chemistry
MOAC DTC, Senate House
University of Warwick,
Coventry, United Kingdom