Designing a protocol to fast-track research into a new cancer drug target

Posted by on 13 February 2023

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Summary of Research - December 2022

by Victoria Gibbs, Massey University

22 Gibbs PhotoAotearoa has an ageing population. Whilst the process of ageing reflects the growth in knowledge and character that comes with life, it also brings with it new challenges. Cancer is a disease that is more prevalent in our older population. Not only does cancer reduce the lifespan of patients, but it reduces their quality of life, making it trying for both patients and their loved ones. Many currently available anti-cancer treatments are themselves hard on the patient and are often unable to provide complete remission. It is important to develop new treatments that will provide better outcomes for cancer patients.

The cellular protein GCN2 is exploited by cancer cells to help their growth and treatment resistance. The Sattlegger group are investigating the interaction-point between GCN2 and a crucial supporting protein (SP) as a target for a drug to inhibit GCN2 activity and curb cancer growth. A drug targeting this region would have few side-effects as its only known function is in GCN2 regulation, making it a prime candidate for research. This interaction has been most well-studied in yeast due to the ease with which this organism can be manipulated.

My Masters project involved setting up a yeast two-hybrid system (Y2HS) whereby we can study GCN2 and SP in yeast cells to fast-track research into this interaction. During the course of the year, I was privileged to be able to upgrade my Masters research into a PhD project. This means that I will conduct a more thorough investigation than initially outlined and will result in more informative results. Using the Y2HS I set up I will be able to express different peptides to see what parameters are able to block this interaction. This will provide a strong foundation for future drug design.

Over the course of the year I have become proficient at the techniques necessary to carry out my research. This has allowed me to test making several experimental fragments and fine-tune this design to improve the effectiveness of production. I am now in the process of acquiring these constructs from a company to ensure they are of the highest quality while we continue to optimize our in-house methods for future production. I anticipate my first Y2H tests to be underway in a month.

At the same time, I have been developing yeast strains with various protein deletions to limit background interference in our Y2H tests. This will increase the sensitivity of my Y2HS which will make gauging the influence of binding factors in my PhD work more informative.

Finally, I have been able to conduct an in-depth analysis of the current literature and structures to fully appreciate the features of GCN2 and SP that are known or likely to mediate this interaction. This work lays a strong foundation for my later experiments which aim to narrow down the binding region and identify how we can increase binding strength, which will provide critical information for drug design.

I am truly grateful to the HOPE Foundation for Research on Ageing and all its sponsors for the support this scholarship has given me to embark on this project. Your contribution to research is crucial to helping us learn more about ageing and improving the lives of many.

Ngā mihi maioha; thank you.

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