Understanding intrinsically disordered proteins and their potential as new drug targets through novel measurement capabilities
Lead Research Organisation:
University of Strathclyde
Department Name: Pure and Applied Chemistry
Abstract
My research focuses on studying a type of proteins called intrinsically disordered proteins to find new drug targets. Unlike most proteins that exist in a defined 3-dimensional structure, IDPs switch quickly between multiple shapes. This renders them notoriously difficult to study. IDPs are involved in diseases such as cancer and neurodegenerative diseases, but their dynamic behaviour makes them challenging to study using traditional methods.
I use a technique called ion mobility-mass spectrometry (IMMS), which is effective for analysing IDPs. This method helps me understand the different shapes these proteins can take, even the temporary ones. It's also useful for figuring out how proteins interact with each other or with drugs.
In the initial three years of my Fellowship, I demonstrated that IMMS is effective for characterising IDPs based on their range of shapes, and for understanding how they change when a drug is involved. I've also showed that IMMS can help us understand how IDPs change when they undergo a process called liquid-liquid phase separation (LLPS), which is important in both normal cell function and disease.
For the next phase of the Fellowship, the main goals are as follows:
1. To develop faster IMMS methods to quickly screen large sets of molecules for potential new drugs that could target an IDP of interest
2. Use newly developed methods to investigate how the shapes of IDPs change during LLPS, especially focusing on a protein related to prostate cancer.
To achieve the first goal, I will continue to collaborate with Waters, an IMMS vendor that is dedicated to advancing instrumentation. We'll use a novel device to quickly test a variety of compounds to see which ones interact with the IDP and change its shape. The specific protein we're looking at is important in advanced stages of prostate cancer.
For the second goal, we aim to further understand how IDPs change shape during LLPS, particularly in the context of prostate cancer. We'll investigate how a molecule that is known to disrupt this process affect the shape distribution of the androgen receptor, which is the key protein involved in prostate cancer. The ultimate aim is to develop strategies to interfere with this process and potentially treat advanced prostate cancer.
In summary, my research aims to develop novel techniques to study IDPs and find new ways to target them for medical purposes.
I use a technique called ion mobility-mass spectrometry (IMMS), which is effective for analysing IDPs. This method helps me understand the different shapes these proteins can take, even the temporary ones. It's also useful for figuring out how proteins interact with each other or with drugs.
In the initial three years of my Fellowship, I demonstrated that IMMS is effective for characterising IDPs based on their range of shapes, and for understanding how they change when a drug is involved. I've also showed that IMMS can help us understand how IDPs change when they undergo a process called liquid-liquid phase separation (LLPS), which is important in both normal cell function and disease.
For the next phase of the Fellowship, the main goals are as follows:
1. To develop faster IMMS methods to quickly screen large sets of molecules for potential new drugs that could target an IDP of interest
2. Use newly developed methods to investigate how the shapes of IDPs change during LLPS, especially focusing on a protein related to prostate cancer.
To achieve the first goal, I will continue to collaborate with Waters, an IMMS vendor that is dedicated to advancing instrumentation. We'll use a novel device to quickly test a variety of compounds to see which ones interact with the IDP and change its shape. The specific protein we're looking at is important in advanced stages of prostate cancer.
For the second goal, we aim to further understand how IDPs change shape during LLPS, particularly in the context of prostate cancer. We'll investigate how a molecule that is known to disrupt this process affect the shape distribution of the androgen receptor, which is the key protein involved in prostate cancer. The ultimate aim is to develop strategies to interfere with this process and potentially treat advanced prostate cancer.
In summary, my research aims to develop novel techniques to study IDPs and find new ways to target them for medical purposes.
