Professor Mibel Aguilar

Biochemistry & Molecular Biology

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Short biography

Professor Mibel Aguilar is a Bioanalytical and Biophysical Chemist at Monash University working across many disciplines and now specialising in research focuses on biomembrane nanotechnology and peptidomimetic drug design. She completed her PhD in Chemistry at the University of Melbourne studying the metabolism and toxicity of paracetamol. She then completed a Post Doctoral position at St Vincent's Institute for Medical Research working on developing physical models for protein analysis and purification. She then moved to Monash University where her group now focuses on peptide-based drug design and biomembrane nanotechnology and are developing novel compounds that allow us to exploit the potential of peptides as drugs. She has published 164 papers and 24 book chapters, and edited a volume of Methods in Molecular Biology on HPLC publications. She has supervised several PhD and Honours students.

Profile

I have 30 years experience in the peptide structure and function and peptidomimetic design and we are currently applying this research to:

  1. The design of peptide-based materials as molecular nanowires and scaffolds for tissue engineering and
  2. Biomembrane engineering as platforms for artificial cells

Together with Professor Perlmutter, (School of Chemistry) we have pioneered the application of beta amino acids in the development of potent and proteolytically-resistant peptidomimetic drug candidates. We have published 22 papers together and our review in Curr Med Chem has been cited 216 times. We were also the first to demonstrate beta-peptides as high affinity T-cell epitopes for peptide-based vaccines. More recently, we have reported the first synthesis of novel beta amino acids which when incorporated into beta peptides allows the design of novel functional biomaterials. The application of our peptidomimetic strategy to the design of novel biomaterials is the basis of the current proposal and is underpinned by a range of projects in my laboratory as evidenced by my publication list.

My research also focuses on the design and development of immobilized lipid materials and biosensor analysis of membrane peptides and proteins. In the broader field of membrane biophysics, my group has also pioneered new techniques to measure the affinity of peptides for different phospholipids using immobilised lipid chromatography and surface plasmon resonance. Used in combination, these techniques allow the binding affinity, kinetics of binding and the relative contribution of electrostatic and hydrophobic forces to membrane binding. While this data is critical to understanding the mechanism of peptide and protein-membrane interactions, it was relatively difficult or time-consuming to generate by existing techniques.

I have also contributed significantly to the field of amyloid structure and function with a specific focus on neurodegenerative diseases. In collaboration with Professor David Small, we have pioneered the application of membrane-mimetic technology to understanding the molecular basis of amyloid formation and the role of surface interactions. We have co-published 19 papers and 4 book chapters, with a specific focus on b-amyloid (Alzheimer's Disease) and transthyretin (familial amyloidotic polyneuropathy). We were the first to explore the membrane interactions using optical biosensors, and have published 7 papers in this field including Biochemistry, J Neurochem and FEBS J. Together with Dr Mechler, we were also the first to report the direct visualisation of a single molecule of Ab1-40 using high resolution scanning tunnelling microscopy resulting in 5 papers including J Struct Biol, Biopolymers and Biomaterials and 1 recent paper on the detection of early-stage intermediates of Ab.

Recent relevant publications

  • Del Borgo MP, Mechler* AI, Traore D, Forsyth C, Wilce JA, Wilce MCJ, Aguilar MI* and Perlmutter* P, 'Supramolecular Self-Assembly of N-Acetyl capped b-Peptides Leads to Nano-to Macroscale Fibre Formation'. Angewandte Chemie Int Ed.. 2013, 52 8266-8270.
  • Hirst D, Lee TH, Swann MJ, and Aguilar MI, 'Multi-state kinetic analysis of antimicrobial peptide-membrane interactions', Anal Chem., 85 (2013) 9296−9304.
  • Lee TH, Heng C, Separovic F and Aguilar MI, 'Comparison of Reversible Membrane Destabilisation Induced by Antimicrobial Peptides Derived from Australian Frogs', Biochim Biophys Acta (Biomembranes), 1838 (2014) 2205-15.
  • Andreu-Fernández V, Genoves A*, Lee TH, Stellato M, Lucantoni F, Orzáez, M, Mingarro,I, Aguilar MI* & Perez-Payá, E, 'Peptides derived from Transmembrane (TM) domains of diverse Bcl-2 proteins exert disruptive behavior in mitochondrial membranes'. ACS Chem Biol, accepted June 3, 2014.
  • Hall, K, Lee TH, Mechler A, Swann MJ and Aguilar MI, 'Real-time Measurement of Multiple Membrane Conformational States During Antimicrobial Peptide Binding: The Balance Between Recovery and Lysis'. Scientific Reports, June 27 4:5479 (2014).

MIME Theme

  • Peptide-based biomaterials as molecular nanowires and scaffolds for tissue engineering
  • Biomembrane engineering as platforms for artificial cells