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Aguilar Lab research

CollaborationsStudent research projects | Publications

About Professor Mibel Aguilar

I am a Bioanalytical and Biophysical Chemist and my research focuses on biomembrane nanotechnology, peptidomimetic drug design and biomaterials for regenerative medicine. I completed my PhD in Chemistry at the University of Melbourne studying the metabolism and toxicity of paracetamol. I then completed a Post-Doctoral position at St Vincent’s Institute for Medical Research working on developing physical models for protein analysis and purification. I then moved to Monash University where my group now focuses on developing novel compounds that allow us to exploit the potential of peptides as drugs. Our membrane nanotechnology projects involve the development of new biosensor methods for the analysis of membrane-mediated processes such as apoptosis, G protein-coupled receptor function and antimicrobial peptide function. Our biomaterial research focuses on the design of new treatments for stroke, kidney disease, pelvic organ prolapse and neurodegenerative diseases.


Our research

Current projects

  • Peptide-based drug design
  • Biomaterials for regenerative medicine
  • Mechanism of resistance to antimicrobial peptides
  • Role of the mitochondrial membrane in apoptosis

Visit Professor Aguilar's Monash research profile to see a full listing of current projects.

Peptide-based drug design

The use of peptidomimetics has emerged as a powerful means for overcoming the limitations inherent in the physical characteristics of peptides thus improving their therapeutic potential. A peptidomimetic approach that has emerged in recent years with significant potential, is the use of β-amino acids. β -Amino acids are similar to β-amino acids in that they contain an amino terminus and a carboxyl terminus. However, in β-amino acids two carbon atoms separate these functional termini. β-amino acids, which results in a total of 4 possible diastereoisomers for any given side chain. The flexibility to generate a vast range of stereo- and regioisomers, together with the possibility of disubstitution, significantly expands the structural diversity of β-amino acids thereby providing enormous scope for molecular design. The incorporation of β-amino acids has been successful in creating peptidomimetics that not only have potent biological activity, but are also resistant to proteolysis and we are applying these techniques to a range of protein targets.

Design templates used in our bioactive peptide projects

Read about the recent publications for Peptide-based drug design

Design of novel antifibrotics

Cardiovascular disease (CVDs) is the leading cause of mortality globally and accounts for 17 million deaths annually and one death in every two seconds worldwide. These conditions often lead to accumulation of excessive collagen in the organs such as the heart and kidneys, which is also referred to as fibrosis. Fibrosis can often lead to organ damage and dysfunction and targeting organ fibrosis is thus important in improving patient outcomes and novel treatment for CVDs is urgently needed. The angiotensin type 2 receptor (AT2R) is upregulated in many CVDs conditions and mediates cardio-protective effects in diseased animal models. We have a large program aimed at developing novel AT2R selective peptide ligands to investigate the potential anti-fibrotic effects of these peptides in both heart and kidney.

Ligands for AT2R receptor control

Self-assembled peptide-based materials

We have an intensive research program based upon our discovery that peptides comprised entirely of beta-amino acids are able to spontaneously self-assemble into fibres. This self-assembly is based upon the unique secondary structure of beta-peptides which affords a sequence independent self-assembly. Moreover, the sequence independent head-to-tail self-assembly of β-peptides, means that these peptides can be decorated with specific motifs without affecting their ability to form fibres. In particular, β-peptides can be functionalised with a fatty acid to spontaneously form shear thinning hydrogels. Furthermore, many β-tripeptide monomers can be combined into the one pot to afford either hydrogels or nanofibres with tunable function and no loss of self-assembly.

Read about the recent publications for Peptide-based materials

Biomembrane biophysics

I) Mechanism of resistance to antimicrobial peptides

Antibiotic resistance continues to emerge and intensify and while antimicrobial peptides (AMPs) are a promising alternative to current antibiotics, bacteria have also evolved a range of resistance mechanisms to AMPs, which include thickening of the cell wall, modification of the phospholipid composition, changing the net surface charge, increasing the membrane fluidity, releasing proteinases to degrade the peptides and discharging amino acids into the environment to reduce hypo-osmotic stress. Our research aims to characterise how bacteria transiently modify their lipid content and repel the action of AMPs and how the membrane barrier can be more effectively targeted with agents tailored to lyse compositionally different membranes.

Interconnection between membrane structure and peptide function

II) Role of the mitochondrial membrane in apoptosis

The Bcl-2 family of proteins is crucial for apoptosis (a form of programmed cell death) regulation and in spite of the recognised importance of the membranes in the function of Bcl-2 family members, this process is still poorly understood. The overall aim of this project therefore is to perform a systematic evaluation of the membrane interactions of the Bcl-2 family of proteins in complementary biophysical and cellular experiments. Our research aims to redefine the mechanism of apoptosis and provide new avenues for the development of compounds to selectively modulate diseases in which apoptosis is dysregulated.

Mitochondrial membrane permeabilization to control cell growth

Read about the recent publications for Biomembrane biophysics


Collaborations

We collaborate with many scientists and research organisations around the world. Some of our more significant national and international collaborators are listed below. Click on the map to see the details for each of these collaborators (dive into specific publications and outputs by clicking on the dots).

Lipidomics and antimicrobial resistance
Professor Frances Separovic and Professor Gavin Reid (University of Melbourne)

Antimicrobial cyclic peptide action
Professor Jose Martins (University of Ghent)

Design of novel antifibrotics
Professor Rob Widdop (Monash BDI, Pharmacology)

Self-assembled peptide-based materials

Customised hydrogels for delivery of therapeutics
Dr Mark Del Borgo and Dr Ketav Kulkarni

Creating novel optoelectronic nanomaterials
Dr Ketav Kulkarni and Dr Mark Del Borgo

Next generation neural devices
Assoc Prof John Forsythe (Monash University, Materials Engineering) & Prof Helena Parkington (Monash BDI, Physiology)

Kidney and diabetes
Professor Sharon Ricardo (Monash BDI, Anatomy & Developmental Biology)

New treatments for stroke
Dr Brad Broughton (Monash BDI, Pharmacology) and Assoc Prof John Forsythe (Monash University, Materials Engineering)

Structure-based design
Professor Louise Serpell (Sussex) and Professor Irene Yarovksy (RMIT)


Student research projects

The Aguilar Lab offers a variety of Honours, Masters and PhD projects for students interested in joining our group. There are also a number of short term research opportunities available.

Please visit Supervisor Connect to explore the projects currently available in our Lab.