Protein science and its impact on drug discovery

Protein science and its impact on drug discovery

In this interview conducted at SLAS EU 2023 in Brussels, Belgium, we speak to Mark Abbott, Managing Director of Peak Proteins, about protein science and its importance in drug discovery.

Please, can you introduce yourself and tell us what inspired your career in protein and cell science?

I’m Mark Abbott, Managing Director of Peak Proteins, part of Sygnature Discovery, an integrated contract research organisation.

As a college student, I enjoyed experimenting, not knowing the outcome, and solving problems. This led to a Ph.D. Postdoctoral work on membrane receptors and carbohydrate-binding proteins.

I love the research challenge of understanding and solving protein problems. This led to a full career working with proteins respectively.

The term “proteomics” is an umbrella term for the structure, function, and biochemical significance of proteins. How has this field changed over the past 20 years, and what makes it an exciting sector of drug discovery?

Some of the techniques we use today are more than half a century old, for example, ion exchange, size exclusion chromatography, and SDS-PAGE. Some processes have changed dramatically, such as gene synthesis, increased use of automation for techniques such as protein crystallization, and the much greater deployment of cryoEM. Together, these factors have rapidly increased our ability to solve protein structures. But, of course, protein crystallography itself is much older. Fred Sanger won the Nobel Prize in 1958 for the crystal structure of insulin.

However, protein science has constantly evolved so that what we are doing now has been completely revolutionized by evolution.

What are the industrial applications of protein science?

Proteins are regularly targets for drug discovery. Trying to find a new treatment for cancer often focuses on the abnormal protein in the disease process. Likewise, over the past 30 years, proteins have essentially become drugs in their own right. The ability to make proteins as drugs on a very large scale is becoming critical.

Image credit: Christoph Borgstedt/Shutterstock.com

Image credit: Christoph Borgstedt/Shutterstock.com

Cryo-EM has become very important and is now starting to influence protein science in the drug discovery process. Gene synthesis, which began to develop 20 years ago, now underpins much of protein science. The influence of artificial intelligence is growing rapidly.

The basis of all this is the ability to make high-quality proteins, which are still based on traditional techniques. The ability to make and detect this protein is crucial in drug discovery.

You are the chair of the session “Protein Science” at SLAS EU 2023. Please, can you introduce us to the speakers in the session, as well as the topics covered?

There are three speakers in the session, the first is Praveen Mahajan, who works for Astex Pharmaceuticals in the UK. Astex is one of the leading companies exploiting structural biology, crystallography, and cryo-EM, to support and drive drug discovery.

Secondly, we have Magdalena Richter, who works for AstraZeneca. Magdalena’s talk covers hydrogen and deuterium exchange along with mass spectrometry and how AstraZeneca is using this technology to understand protein structures.

The third speaker is Su Jerwood from Exscientia. Her talk discusses the statistical approach to understanding experiments, processes, and assays. Sometimes scientists are a bit skeptical of statistics, but I’ve seen them successfully exploited.

Throughout your career, you have led projects and published more than 30 peer-reviewed publications on proteomics in drug discovery. How have you seen the relationship between protein science and drug discovery change throughout your career?

When I started my career, recombinant DNA technology was in its infancy. Even biochemical screening of drugs uses only raw tissue and radioactive cross-linking assays.

However, you can now order hundreds of variants of synthetic genes and run many parallel screens against a given target. You can precisely design how the display operates using recombinant DNA technology and back this up with highly detailed, high-resolution structural biology. It was all an evolution, but the result was a revolution.

Image credit: Gorodenkov/Shutterstock.com

Image credit: Gorodenkov/Shutterstock.com

Given your experience, how do you expect the field of proteomics in drug discovery to change in the next decade? What are the main challenges the field will face at this time?

I think AI is still in its infancy in terms of its impact on protein science and drug discovery. Although others are better informed to comment on this, I realize that AI is starting to impact what we do significantly, and that many of our clients are well invested in AI.

The second technology that will become increasingly important is cryo-EM, especially in drug discovery. I suspect that the ability to go through the process faster will also increase. The key to this will continue to be the ability to produce very high quality proteins.

SLAS is an international professional society that aims to transform research by promoting collaboration at the intersection of science and technology. Why is this collaboration important for global drug discovery and medicine?

Collaboration in drug discovery is crucial. Even major global pharmaceutical organizations like AstraZeneca, although they have entirely in-house projects, are also involved in a lot of collaboration.

The ability to foster this collaboration at meetings like SLAS is crucial. Scientists are smart, curious people, and collaboration fuels this entire process.

Revolution by evolution: protein science and its impact on drug discovery

You are the founder and managing director of Peak Proteins, a British biotechnology company. Why is it so important for SLAS EU to recognize the quantity and quality of business here in Europe?

Before this conference, I watched an interview with Steve Rees of AstraZeneca, who commented on how COVID-19 vaccines were not invented in nine months but through investment from the past decade in basic science and technology. Much of this investment has been within Europe, both in industry and academia.

Continuing this investment within Europe is extremely important

With partnerships being key to accelerating scientific research, how important are in-person conferences like SLAS in strengthening cross-sector relationships, especially between academia and industry?

Relationships with customers, suppliers and collaborators support our business. Our business is about solving protein-related problems for our clients so they can advance their business. In-person conferences are an important part of building relationships. We always have difficult projects where you try to anticipate what will happen, but after the first experience, even the best laid plans can fall apart.
We love these types of projects where things don’t go as planned, and you have to look at the data and the literature and talk to the client and try to solve those problems.

What’s next for you and your business? Are you involved in any exciting upcoming projects?

There are two conferences we will likely attend this year. The first is PSDI (Protein Structure Determination in Industry). As a large structural biology company, we will have a presence.

Secondly, we will be attending the ELRIG Drug Discovery Conference in Liverpool later this year.

About Mark Abbott

Dr. Mark Abbott spent more than 20 years working as a protein biochemist at AstraZeneca, where he was involved in the discovery of small molecules and biologics. He left in 2014 and founded Peak Proteins, a CRO firm serving industrial and academic clients globally.

Initially just two people, it has now grown to about 50 people with skills in protein expression and purification, protein biophysics, and protein structural biology, including X-ray and cryoEM. Peak Proteins was acquired by Sygnature Discovery (an integrated CRO drug discovery company) in April 2022 and is now fully part of that organization. A long career fueled by an ongoing enthusiasm for tackling difficult proteins!

    (Tags for translation) Drug discovery 

You may also like...

Leave a Reply

Your email address will not be published. Required fields are marked *