By Nautilus Biotechnology
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The podcast currently has 12 episodes available.
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
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:
*Small edit on Sarah's background - She did her graduate work at Washington University in St. Louis and a Postdoc at Massachusetts General Hospital*
Chapters00:00 – 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
ResourcesDominant 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 to Alzheimer’s Disease (Hurst et al. 2023)
o Paper linking the NRN1 protein to cognitive resilience in Alzheimer’s
o Nautilus blog post about this paper
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss the challenges and opportunities of plasma proteomics. Their conversation focuses on:
· Why blood plasma may be a good source of protein biomarkers
· Current methodologies and pitfalls in plasma proteomics
· The path forward for plasma proteomics
What is Plasma Proteomics?For those who are new to this topic, plasma is the liquid portion of the blood distinct from fractions containing red and white blood cells. Given the relatively non-invasive ways physicians can collect patient plasma, and the blood’s intimate association with tissues throughout the body, plasma is potentially an excellent source of protein biomarkers. Yet, it is quite difficult to measure the levels of all plasma proteins because their concentrations span over 12 orders of magnitude. This episode features an in-depth discussion of the ways plasma proteomics efforts have and have not lived up to the promise of biomarker discovery and what we can do to advance plasma biomarker discovery efforts in the future.
Chapters00:00 – 01:01 – Intro
01:02 – 4:55 – What is the promise of plasma proteomics?
04:55 – 07:23 – Is the plasma proteome really the best source of biomarkers?
07:23 – 10:16 – How do proteins get into the blood and what are the implications for biomarker discovery?
10:16 – 13:59 – Is it clear that proteins are the best candidates for blood biomarkers?
13:59 – 19:57 – Advances in and the future of comprehensive plasma proteomics
19:57 – 22:31 – Pros and cons of fractionating the plasma proteome to discover biomarkers
22:31 – 28:14 – Progress in identifying multiomic plasma biomarkers and the path forward
28:14 – End – Outro
ResourcesNano-omics: nanotechnology-based multidimensional harvesting of the blood-circulating cancerome (Gardner et al. 2022)
o Review from focused on the development multiomics liquid biopsies
Multicompartment modeling of protein shedding kinetics during vascularized tumor growth (Machiraju et al. 2020)
o Work from Parag’s Lab investigating tumor protein shedding
Simulation of the Protein-Shedding Kinetics of a Fully Vascularized Tumor (Frieboes et al. 2015)
o Tumor protein shedding work from Parag’s Lab
Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations (Hori and Gambhir et al. 2011)
o Study modeling how much protein could be shed and detected from different size tumors
The human plasma proteome: history, character, and diagnostic prospects (Anderson and Anderson 2002)
o Review discussing the clinical importance of the plasma proteome and the wide range of protein abundance in the plasma proteome
Blood Biomarkers to Detect Alzheimer Disease in Primary Care and Secondary Care (Palmqvist et al. 2024)
o An example of the potential power of blood plasma as a source of biomarkers
Plasma Proteome Project
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
Proteins adopt a wide variety of functions depending upon factors like their location in the cell, their modifications, and the biomolecules they interact with. While many of us may have been taught that single genes produce single proteins that have single functions, protein function is far more dynamic than that. In this episode of Translating Proteomics, Nautilus Co-Founder and Chief Scientist Parag Mallick sits down with University of Cambridge Professor and proteomics expert Kathryn Lilley to discuss our evolving understanding of protein function. They cover:
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
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:
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
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 [email protected]!
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 [email protected]!
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:
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
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 [email protected]!
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:
Learn more about biomarkers.
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Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to [email protected]!
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:
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The podcast currently has 12 episodes available.
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