Translating Proteomics – Details, episodes & analysis

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

Despite incredible leaps in our understanding of molecular biology, the majority of drug development efforts still fail, and those that succeed often fail to return investment dollars. Proteomics has the potential to change that by providing high-resolution views of the biochemical drivers of biological function - proteins. In this episode of Translating Proteomics, Parag and Andreas discuss how proteomics can help researchers identify good drug targets, personalize drug development, and advance precision medicine.

Chapters:

00:00 - How do we define good drug targets and "druggable" in the age of proteomics

08:16 - Advancing personalized medicine through proteomics

10:58 - How proteomics technologies have changed drug development

15:13 - New abilities next-generation proteomics technologies give us in drug development

Learn about proteomics and biomarker discovery:

https://youtu.be/8rcAxHSRGYs?si=kZ0UX42TJ8tWIaSN

Learn more about proteomics and precision medicine:

https://youtu.be/bzRlM45agBY?si=eop2XcGLc_oLeiVc

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

Proteins are far more than just the output of genes. They can be modified in myriad ways to produce millions of proteoforms with altered dynamics, localization, and function. For a comprehensive understanding of biology that will propel drug development and biomarker discovery forward, we need to be able to measure proteoforms routinely. In this episode, Parag and Andreas discuss the incredible value that will come from studying proteoforms and describe what it will take to make proteoform measurement a routine part of biology research.

Chapters:

00:00 - Introduction to proteoforms

09:38 - Evidence that proteoforms are important and how we can use proteoform data

19:28 - Technology advances needed to understand proteoform biology

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

AI might be the biggest buzz word of the decade, but the buzz is warranted in terms of its practical potential in biological research. In this episode of Translating Proteomics, Parag and Andreas discuss some of the early wins for AI in biology, practical ways AI can be applied to biology research in the near term, challenges in that application, and how proteomics researchers in particular can use AI to advance their work.

Chapters:

• 00:00 – Why now is the time to apply AI to biomedicine
• 05:28 – Difficulties and potential solutions when applying AI to biology
• 14:20 – How AI will impact the study of proteins
• 19:34 – Risks of AI in biomedicine

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

From high school biology on up, we're taught the central dogma of biology - that biological information flows from DNA to RNA to proteins. This representation of the central dogma is, however, very much a simplification of its original formulation by Francis Crick and over-applying it can lead us down spurious paths and faulty conclusions. In this episode of Translating Proteomics, Parag and Andreas dive into the real meaning of the central dogma and discuss how modern biology research, including proteomics, shows we must drastically alter the ways we use and interpret the central dogma.

Chapters:

00:00 – What is the central dogma and how is it misinterpreted?

08:06 – Regulation and control in biology

11:58 – The need for new models in biology

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

Protein biomarkers are proteins measured as indicators of biological processes. People often hope biomarkers will take the form of elevated or decreased amounts of single proteins, but few single protein measurements provide specific and sensitive indications of biological processes. In this episode of Translating Proteomics, Parag and Andreas discuss why it is difficult to find new biomarkers and describe how new techniques can enable the development of multi-protein, multi-time point, and even multiomic biomarkers that have more potential than any single protein measurement.

Some key points of discussion:

• Biomarkers are difficult to find because of the methods we use to find them and because there is a ton of variability in natural biological systems
• Most proteins are biomarkers
• We need more proteome-scale data over space and time to find new biomarkers

Learn more about biomarkers.

Let us know what you think about the podcast.

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

It's no surprise that biological systems change dramatically over space and time, but we often ignore these dynamics when comparing biological samples. In the latest episode of Translating Proteomics, Parag and Andreas discuss why it's essential to take space and time into account and envision ways we can design experiments that explicitly incorporate spacial and temporal considerations.

Chapters:

00:00 - Biological systems as dynamic, adaptive systems

04:45 - How current experimental designs rarely take space and time into account

11:54 - The tools necessary to sufficiently measure biology in space and time

Some key takeaways from the conversation:

• Different biological processes occur at very different time scales
• Complex, multiomic interactions can only be understood over time and space
• We need to properly collect, annotate, and share omics-level data in order to understand the rules that govern complex biology

Let us know what you think about the podcast.

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

Sure, proteomics may revolutionize precision medicine and biomarker discovery, but did you know it can help make better cheese? Listen to the latest episode of our new series, "Translating Proteomics" featuring Nautilus Co-Founder and Chief Scientist, Parag Mallick, and Nautilus Senior Director of Scientific Affairs and Alliance Management, Andreas Huhmer to learn the many ways we can put the proteome to work as the proteomics revolution begins to bear fruit.

Let us know what you think about the podcast.

Learn more about applications of proteomics

In this episode, Parag mentions work from Matthias Selbach's Lab. Learn more about the Selbach Lab here.

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

The idea to measure the proteome to get a clear understanding of healthy and diseased tissues at the molecular level has been around for many years but has not come to fruition in a broadly accessible and applicable way. In this episode we discuss:

• Why now is the time to make this goal a reality
• Why past efforts to broadly leverage proteomics did not work out
• What we've learned from the past
• What's changed in proteomics and science in general that makes a proteomics breakthrough possible

Learn more about proteomics

Let us know what you think about the podcast.

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

In our Translating Proteomics episode titled "Harnessing Proteoforms to Understand Life's Complexity", Parag and Andreas discussed why proteoforms are important in a theoretical sense. In this episode, Parag sits down with Northwestern University Professor and proteoform pioneer, Neil Kelleher to dive deep into the biology of proteoforms. They cover:

• What proteoforms are
• Examples of the importance of proteoforms
• The scale of and technological advances needed to meet the challenges of proteoform biology.

• Recent work from Neil's lab showing blood proteoforms can help predict liver transplant success (Melani et al. 2022).
• Work form Ying Ge's lab showing changes in troponin proteoforms correlate with varying degrees of heart disease (Zhang et al. 2011).
• The BioTyper - a mass spectrometry-based device that can identify different kinds of microbes.

• The Human Proteoform Atlas webpage
• Publication describing The Human Proteoform Atlas (Hollas et al. 2022)
• Publication discussing how many human proteoforms there are (Aebersold et al. 2018)
• Animation - Proteoform Analysis on the Nautilus Proteome Analysis Platform

Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio!

On this episode of Translating Proteomics, host Andreas Huhmer discusses advances in Alzheimer’s research with special guest and Curie Bio Drug Maker in Residence, Sarah DeVos Ph.D. Their conversation focuses on:

• The impact of molecular diagnostics on Alzheimer’s research
• Recent Alzheimer’s drug approvals
• The future of Alzheimer’s research

*Small edit on Sarah's background - She did her graduate work at Washington University in St. Louis and a Postdoc at Massachusetts General Hospital*

00:00 – Introduction

01:54 – Why Sarah began studying Alzheimer’s

03:39 – Current tools and needs for future Alzheimer’s diagnostics

09:52 – Recent drug approvals in the Alzheimer’s space and their relationship to diagnostics

14:26 – Is it possible to develop biomarkers that detect Alzheimer’s at its earliest stages?

16:36 – What is limiting the development of new Alzheimer’s biomarkers?

17:51 – The DIAN trials and learnings from studying dominantly inherited Alzheimer’s

19:33 – The genetics of Alzheimer’s

22:19 – Novel approaches to identifying and understanding Alzheimer’s pathology 

25:54 – Where can proteomics advance Alzheimer’s research?

31:25 – The role of proteomics in Alzheimer’s animal models

34:33 – Sarah’s hopes for the next 10 years of Alzheimer’s research

41:39 - Outro

Dominant Inherited Alzheimer’s Network (DIAN) trials research updates

o   In the DIAN trials, researchers work with families to study various clinical and basic science aspects of dominantly inherited Alzheimer’s disease.

Amyloid plaque reducing clinical trials:

o   Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer's Disease (Haeberlein et al. 2022)

o   Donanemab in Early Symptomatic Alzheimer Disease - The TRAILBLAZER-ALZ 2 Randomized Clinical Trial (Sims et al. 2023)

o   Lecanemab in Early Alzheimer’s Disease (Van Duck et al. 2022)

Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Car (Palmqvist et al. 2024)

o   Clinical research into a new phospo-tau biomarker that can help physicians more effectively diagnose Alzheimer’s disease

Resurrecting the Mysteries of Big Tau (Fischer and Baas 2021)

o   Review covering a potentially neuro-protective form of tau called “Big tau”

Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience...