Peptide research aims to ‘divide and rule’ cancer cells

Translating complex concepts and years of research into everyday English is difficult but when English is not your first language and you have only three-minutes to do it, it’s doubly difficult.

  • Research aims to inactive the LDH enzyme cancer cells depend on to multiply
  • Peptides being designed to break up the proteins in LDH
  • The peptide must be modified to target cancer cells only

Not so, for Spain’s Ferran Nadal-Bufi who has won QUT’s annual Three-minute Thesis competition and also taken out the People’s Prize for his clear and engaging video explaining his PhD research into the emerging area of peptide therapeutics for fighting advanced cancer.

Mr Nadal-Bufi’s interest is in cancer cell membranes, in particular, ways to deliver peptide-based drugs through these membranes.

He aims to cut off the cells’ energy supply using a novel strategy he describes as ‘divide and rule’ to inactivate the enzyme that cancers cells depend on to grow and multiply using a peptide initially isolated from a Brazilian spider.

As he explains it: “Our cells need energy to work and most of the energy comes from oxygen but a small portion of the energy doesn’t require oxygen and is kept for emergencies and high energy needs such as sprinting for the bus or a rally in tennis.

“When a cell becomes cancerous it obtains most of its energy from this non-oxygen (anaerobic) source, using an enzyme called LDH to make energy without oxygen.

“We know if we can inhibit LDH we can stop cancer getting its main source of energy and starve it to death and many studies, even pharmaceutical companies, have tried to develop an inhibitor using a traditional approach of creating molecules to get inside LDH and block it, which so far hasn’t been successful.

“My strategy is to make use of the fact that LDH is made up of four proteins that fit together like a jigsaw puzzle. If we can divide those proteins ‘we rule’ because LDH becomes inactive.

“To achieve that we use a class of ‘mini proteins’ called peptides that bind to other proteins so we are designing peptides that will bind to the LDH proteins in the right spot so the jigsaw puzzle falls apart depriving cancer cells of their main source of energy.

“One challenge is that these peptides are very potent, and we have to build chemical modifications so that the peptides kill the tumour cells only.

Microscopy image of breast cancer cells treated with peptide drugs – the green areas indicate cell death.

“My research is at an early stage, but I hope that it provides a proof of concept to validate this innovative approach to target cancer cells and that it can be published early next year. The kind of target we are working on is a good strategy to at least block this energy pathway, but there are many other things that are telling cancer cells to keep growing and growing.”

When Ferran was deciding to continue to PhD research, his Masters degree supervisor suggested Dr Sónia Henriques in Brisbane, who was researching cancer cell membranes, as a supervisor.

Ferran took the plunge and moved across the world with his fiancée and two cats, to research with Dr Henriques, in QUT Faculty of Health School of Biomedical Sciences based at the Translational Research Institute, with a QUT Postgraduate Research Award (QUTPRA) Scholarship.

Clearly outgoing and a great communicator, Ferran has quickly made friends and has made the best of being unable to return to Spain in July for his wedding because of the pandemic ban on travel: “Yes, we were one of the many weddings that got postponed.

“Of course, the first month after moving to Australia is always going to be tough because you are trying to make friends and everything. I hang out a lot with people from my lab, especially other international PhD students.

“We are all here in the same situation – they are also new to the city and everything, so we are keen to explore Brisbane and its whereabouts.

I’ve been lucky that I play basketball at a local association so it as much as a way of socializing as a sport. I have made some very good friends in basketball as well.”

At 191cm tall, he is a natural.

How to overcome endosomal entrapment of cellpenetrating peptides to release the therapeutic potential of peptides? was published in Peptide Science.

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