Brazilian Wasp Venom Kills Cancer Cells, But Not Healthy Cells

photo credit: Wasp close up. Attila Fodemesi/Shutterstock.

Wasps get their fair share of bad press. They have painful stingers, and they're not as useful (or cute) to us as bees. However, their time to step in the spotlight may be just around the corner: Their venom has been shown to attack cancer cells while leaving healthy cells alone.

The cancer-targeting toxin in the wasp is called MP1 (Polybia-MP1) and until now, how it selectively eliminates cancer cells was unknown. According to new research, it exploits the atypical arrangement of fats, or lipids, in cancer cell membranes. Their abnormal distribution creates weak points where the toxin can interact with the lipids, which ultimately pokes gaping holes in the membrane. These are sufficiently large for essential molecules to start leaking out, like proteins, which the cell cannot function without.

The wasp responsible for producing this toxin is the Polybia paulista. The toxin has so far been tested on model membranes and examined using a broad range of imaging techniques. You can see the team's research results in the Biophysical Journal.

The wasp, Polybia paulista, which produces the venom containing MP1. Professor Mario Palma/Sao Paulo State University.

"Cancer therapies that attack the lipid composition of the cell membrane would be an entirely new class of anticancer drugs," said Paul Beales from the University of Leeds and co-author of the study. "This could be useful in developing new combination therapies, where multiple drugs are used simultaneously to treat a cancer by attacking different parts of the cancer cells at the same time."

In healthy cell membranes, the inner layer (facing the inside of the cell) is packed with phospholipids, including PS (phosphatidylserine) and PE (phosphatidylethanolamine). However, in cancer cells, PS and PE are located on the outer layer of the cell membrane, facing the opposite way. 

To test the different effects of PS and PE's presence on a cell, the scientists examined how the MP1 interacted with model membranes infused with PE and/or PS. The presence of each phospholipid had a destructive effect on the cells. PS increased the chance of MP1 binding to the membrane by a factor of seven to eight. The presence of PE inflated the size of the holes created by the MP1 by a factor 20 to 30.

"Formed in only seconds, these large pores are big enough to allow critical molecules such as RNA and proteins to easily escape cells," said João Ruggiero Neto from São Paulo State University and co-author of the study. "The dramatic enhancement of the permeabilization induced by the peptide in the presence of PE and the dimensions of the pores in these membranes was surprising."

The next stage for this research is to adjust the amino acid sequence of MP1 to see what gives it its selective properties, and to try and refine them. "Understanding the mechanism of action of this peptide will help in translational studies to further assess the potential for this peptide to be used in medicine," Beales says. "As it has been shown to be selective to cancer cells and non-toxic to normal cells in the lab, this peptide has the potential to be safe, but further work would be required to prove that."

ORIGINAL: IFLScience

by Caroline Reid

September 2, 2015

Luke Bawazer on Genetically Evolving Technology

ORIGINAL: 33rd Square

April 1, 2013 

Synthetic Biology   

Luke Bawazer's research in synthetic biology aims to utilize droplet microfluidics to advance studies of solution-based mineralization and to develop new biomimetic materials engineering strategies. Recently he spoke at TEDxWarwick about the promise and potential of this work. 

Luke Bawazer works in Fiona Meldrum's laboratory at University of Leeds, where he conducts research at the interface of chemistry, materials science, and synthetic biology.

Bawazer's research aims to utilize droplet microfluidics to advance studies of solution-based mineralization and to develop new biomimetic materials engineering strategies. A major anticipated outcome of our research is the ability probe interesting materials chemistry and biochemistry questions that are important to biomineralization, using novel low-cost and high-throughput platforms.

His work is inspired by living organisms, such as bones, teeth, and seashells. These biominerals will help us create new materials technologies using genetic engineering. With synthetic biology we can now make and evolve synthetic genes that encode new inorganic composite materials with useful electronic functions.

"There are many examples in nature of really amazing materials from the perspective of a materials scientist or a materials engineer, they are really amazing materials," Bawazer told Materials Today late last year. "Some examples are abalone shell, which is made of calcium carbonate, or it’s 95% calcium carbonate, and less than 5% organic matter, and yet that composite has a 3,000 times higher fracture toughness than calcium carbonate alone, which is of course just chalk, and it’s due to a unique micro-architecture. So if you examine and look at abalone shell in a microscope, large sections of it look like a brick-and-mortar structure, with micro-bricks in micro-mortar being biomolecules."

Bawazer has recently been highlighted for his work towards genetically evolving semiconductors. He has received his PhD in Biochemistry and Molecular Biology from Dan Morse's laboratory at the University of California focusing on the directed laboratory evolution of biomineralizing enzymes.

According to Bawazwer, "a very important part of this evolution approach is the capacity of these artificial cells, and that’s something I’m very interested in, and that I’d like to develop further. Currently, I’m working with new microfluidic-based techniques to create artificial cells that are more robust, probed in different ways. So, for example, if we’d like to look for materials that are electronically active, then we want to be able to probe these cells electronically, and that requires certain properties of the cell membrane. The main things I’m working on is developing new sets of artificial cells that are more robust and amenable to directed laboratory evolution."

SOURCE TEDx Talks