Translating Proteomics (Nautilus Biotechnology)
Explore every episode of Translating Proteomics
| Pub. Date | Title | Duration | |
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| 05 Jun 2024 | The Future of AI in Biomedicine | 00:24:44 | |
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:
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| 30 Oct 2024 | A New Era In Alzheimer's Research with Sarah DeVos | 00:42:09 | |
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:
*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 Lecanemab in Early Alzheimer’s Disease (Van Duck et al. 2022) 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” | |||
| 28 Oct 2024 | Plasma Proteomics - The Dream and the Nightmare | 00:29:25 | |
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, 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 | |||
| 22 Jan 2025 | Combating the Reproducibility Crisis in Computational Proteomics | 00:28:48 | |
On this episode of Translating Proteomics, co-hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss the reproducibility crisis in biology and specifically focus on how we can enhance reproducibility in computational proteomics. Key topics they cover include: • What the reproducibility crisis is • Factors that make it difficult to replicate multiomics research • Steps we can take to make biology research more reproducible Chapters 00:00 – 01:20 – Introduction 01:20– 03:10 – What is reproducibility in research and why is it important? 03:10 – 05:42 – Recent work from the Mallick Lab focused on computational proteomics reproducibility 05:42 – 09:32 – Ways to help improve reproducibility in computational proteomics – More detailed documentation, moving beyond papers as our main form of documentation, and ensuring computational workflows are available, 09:32 – 11:30 – Why Parag got interested reproducibility – Attempts to build AI layers on top of current workflows 11:30 – 14:00 – The need to create repositories of analytical workflows codified in a structured way that AI can learn from 14:00 – 15:24 – A role for dedicated data curators 15:24 – 18:31 – Moving beyond the idea of study endpoints and recognizing data as part of a larger whole 18:31 – 21:32 – How does AI fit into the continuous analysis and incorporation of new datasets 21:32 – 23:36 – The role of AI in helping researchers design experiments 23:36 – 27:25 – Three things we can do today to increase the reproducibility of computational proteomics experiments: · Be clear about the stated hypothesis · Document analyses through workflow engines and containerized workflows · Advocate for support for funding for reproducibility and reproducibility tools 27:25 – End – Outro Resources Parag’s Gilbert S. Omenn Computational Proteomics Award Lecture o In this lecture, Parag describes his vision for a more reproducible future in proteomics Nature Special on “Challenges in irreproducible research” o A list of articles and perspective pieces discussing the “reproducibility crisis” in research Why Most Published Research Findings Are False (Ioannidis 2005) o Article outlining many of the issues that make it difficult to reproduce research findings Reproducibility Project: Cancer Biology o eLife initiative investigating reproducibility in preclinical cancer research Center for Open Science Preregistration Initiative o Resources for preregistering a hypothesis as part of a study National Institute of Standards and Technology (NIST) o US government agency that aims to... | |||
| 03 Oct 2024 | Are Proteins A Myth? With Special Guest Professor Neil Kelleher | 00:47:35 | |
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:
Some examples of the power of proteoforms covered in this episode
Additional proteoform resources
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| 19 Feb 2025 | Science Communication and Proteomics - Benefits, Barriers, and Solutions with Ben Neely and Ben Orsburn | 00:49:15 | |
On this episode of Translating Proteomics, host Parag Mallick speaks with special guests doctors Ben Neely and Ben Orsburn, leaders in the proteomics community and hosts of “The Proteomics Show” podcast. Their insightful conversation focuses on the role of communication in proteomics and covers: · Impactful things they’ve learned while hosting The Proteomics Show · How their communication efforts have changed their research · Barriers to proteomics becoming more popular in the life sciences and in the broader public Chapters:00:00 – 03:04 – Intro 03:04 – 07:23 – Why the Bens created "The Proteomics Show" 07:23 – 10:42 – Ways the proteomics show has impacted the Bens’ research 10:42 – 16:44 – Every scientist is interesting! 16:44 – 20:36 – Ways the Bens' communication efforts have changed their research 20:36 – 25:08 – Trends in proteomics 25:08 – 35:34 – Barriers to communication between the proteomics community and others in the life science 34:34-48:34 - Barriers to communication between the proteomics community and the broader public 48:34 - End - Outro Resources
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| 26 Jun 2024 | Expanding the Druggable Universe with Proteomics | 00:26:22 | |
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: | |||
| 02 Apr 2024 | Putting Proteomics to Work | 00:16:55 | |
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. | |||
| 08 Jan 2025 | Expanding the Drug Development Toolkit with Proteomics | 00:30:18 | |
On this episode of Translating Proteomics, co-hosts Parag Mallick and Andreas Huhmer of Nautilus Biotechnology discuss how clinical researchers can leverage proteomics for drug development. Some of the themes covered in this episode include: · Proteomics and pre-clinical models · How proteomics can drive patient selection · Choosing the right end points in clinical trials Chapters 00:00 – 01:06 – Introduction 01:06 – 06:51 – Proteomics in pre-clinical studies 06:51 – 11:40 – The importance of choosing the right model for preclinical work 11:40 – 17:10 – How proteomics is used in Phase I/II clinical trials 17:10 – 19:29 – Proteomics tools in patient selection 19:29 – 24:33 – Useful information that we get from proteomics that we can’t get from genomics or transcriptomics 24:33 – 28:14 – Proteomics in Phase III clinical trials and picking the best indications of drug efficacy 28:14 – 29:19 - Understanding why clinical trials fail 29:19 – End - Outro
Resources
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| 04 Dec 2024 | AI and Biotech - The Promise and the Pitfalls with Matt McIlwain and Vijay Pande | 00:53:59 | |
Parag Mallick discusses the role of AI and machine learning in biotech with special guests Vijay Pande from Andreessen Horowitz and Matt McIlwain from Madrona Venture Group. Their fascinating conversation covers:
Chapters 00:00 - Introduction 04:37 - How did Vijay and Matt get into AI and ML 07:33 - The importance of structured data, advances in compute, and algorithmic advances in driving the boom in machine learning 18:44 - The Intersection of AI and biology 21:57 - The evolution of biological models 31:55 - The Complexity of biological data 39:42 - Ways founders and biotech startups are using AI 43:25 - Favorite/Impactful applications of AI/ML 47:00 - AI for experimental design 50:13 - The future of AI in bio/health Resources
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| 08 May 2024 | Single-protein Biomarkers Don't Cut It | 00:21:53 | |
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:
Learn more about biomarkers. | |||
| 02 Apr 2025 | Proteomics Podcast Crossover - The Proteomics Show | 00:48:07 | |
If you listened to our episode focused on science communication featuring proteomics leaders Ben Orsburn Ph.D. and Ben Neely Ph.D., then you've already heard about their excellent podcast, The Proteomics Show. On The Proteomics Show, they interview researchers in the proteomics community to learn about their motivations, their backstories, and their work. Today, we're sharing an episode of The Proteomics Show where the Bens interview Translating Proteomics host Parag Mallick. Check it out to learn about Parag's journey to proteomics, his efforts advocating for open data sharing, and his work as a professional magician. After listening, be sure to check out more episodes of The Proteomics Show on their feed where you'll find over 70 interviews with many, many interesting people in the proteomics community. Find their feed here: https://us-hupo.org/Podcasts | |||
| 24 Apr 2024 | Biology in Space and Time | 00:21:43 | |
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:
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| 02 Apr 2024 | Poised for a Proteomics Breakthrough | 00:17:22 | |
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:
Learn more about proteomics | |||
| 05 Feb 2025 | The Future of Food in a Proteomics World | 00:35:23 | |
On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss the many ways proteomics can impact our interactions with food. Some of the topics they touch upon in this wide-ranging conversation include: · Proteomics and food quality · Proteomics and food safety · Developing new kinds of food with proteomics Chapters00:00 – 01:23 – Introduction 01:23 – 03:27 – Proteomics and alcohol fermentation 03:27 – 05:24 – Food properties and their relationship with molecular composition 05:24 – 07: 42 – How can we use proteoforms to improve food quality? 07:42 – 11:49 – Proteomics to aid plant and animal breeding 11:49 – 14:35 – Proteomics, Food Safety, and Food Security 14:35 – 17:05 – Proteomics and food authenticity 17:05 – 20:36 – Proteomics and terroir 20:36 – 22:48 – Proteomics, the microbiome, and health 22:48 – 24:29 – A fun party trick 24:29 – 30:24 – Creating new foods and flavors 30:24 – 34:33 – Designing food for space 34:33 – End – Outro ResourcesThe post-translational modification landscape of commercial beers (Kerr et al. 2021) · Paper looking at the ways post-translational modification differ between different beers and how protein content relates to the properties of foam · Paper looking at the relationship between proteins and meat tenderness · Research measuring the levels of allergens in different kinds of bread · Study using proteomics to reveal how yeast adapt to growth at different temperatures | |||
| 16 Apr 2025 | Intro to Proteomics | 00:14:45 | |
On this special episode of Translating Proteomics, Parag and Andreas break down the basics of proteomics — perfect for anyone with a background in molecular biology looking to get started in the field. Seasoned experts: We hope you can share this episode as a teaching tool or to inspire others to explore proteomics. Parag and Andreas cover the following questions in the episode, and links to additional Nautilus resources can be found below each question. What is proteomics? What are key questions proteomics can answer?
Why is it important to measure the proteome?
What can and can't you do with proteomics?
What are key proteomics methods and techniques?
What are the major pitfalls when doing proteomics? What are the challenges in proteomic data analysis?
What are people excited about in proteomics?
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| 18 Dec 2024 | 2024 Year-End Special: 3 Exciting Examples of Proteomics Research | 00:51:51 | |
On this special, year-end episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss three of their favorite proteomics publications from 2024. They'll cover one paper in each of the following topic areas:
Synopses of each of the papers can be found below and you can find many more insights in the podcast. Decrypting the molecular basis of cellular drug phenotypes by dose-resolved expression proteomicsIn this work from Professor Bernhard Kuster’s Lab at the Technical University of Munich, researchers assess protein abundance changes that result from treating Jurkat acute T cell leukemia cells with 144 drugs over five drug doses. The researchers use their proteomic data to generate millions of dose response curves for the thousands of proteins measured and discover that the drugs impact many more proteins and pathways than those identified as drug targets. In addition, they checked how 7 of the drug treatments impacted the transcriptome and found there was often discordance between impacts at the mRNA level and the protein level. This works highlights the many ways drugs can impact biological systems and suggests that similar studies will help researchers understand the effects of drug treatments and may even aid in the development of more effective or more specific therapies. Natural proteome diversity links aneuploidy tolerance to protein turnoverAs we discussed on a previous episode of Translating Proteomics, genome alterations often fail to faithfully propagate to the proteome. In this work, researchers from the labs of Professor Judith Berman at Tel Aviv University and Professor Markus Ralser at the Charité - Universitätsmedizin Berlin, investigate the means through which yeast strains adapt to chromosome gains or losses (aneuploidy). They assess the concordance between changes in mRNA and protein expression in aneuploid yeast that were either found in nature or generated in the lab. The researchers observed dosage compensation, a tendency to return to expression levels associated with normal chromosome numbers, for both mRNAs and proteins expressed on aneuploid chromosomes. However, dosage compensation was much stronger at the protein level than the mRNA level and even stronger at the protein level in naturally aneuploid strains compared to lab-generated strains. This work suggests that multiomics efforts are necessary to determine the effects of genomic alterations. In addition, the authors find that protein degradation, as observed through increased ubiquitination, increased turnover of proteins encoded in aneuploid chromosomes, and the up regulation of the proteasome complex, is a key means of dosage compensation. Finally, because the naturally aneuploid strains achieved a higher level of dosage compensation than the lab-generated strains, the authors suggest there has been selection for natural aneuploid strains that down-regulate proteins causing detrimental effects. | |||
| 17 Oct 2024 | Protein Function 201 with Kathryn Lilley | 00:45:40 | |
Do you have a question you'd like answered on a future episode of Translating Proteomics? Send it to translatingproteomics@nautilus.bio! 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:
Research diving into the complexities of protein function
Additional protein function resources
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| 26 Mar 2025 | US HUPO 2025 - Key Takeaways, Trends, and Future Directions for Proteomics | 00:20:49 | |
On this episode of Translating Proteomics, hosts Parag Mallick and Andreas Huhmer discuss their recent experience at the 2025 US Human Proteome Organization conference or US HUPO. Their conversation covers: · The rising use of multiple proteomics platforms · Advances in multiomics And · What they hope to see at the next US HUPO Chapters: 00:00 – Introduction 01:47 – Things Parag and Andreas were most excited about going into US HUPO 06:19 - Trends Parag observed at US HUPO · A bifurcation between studies that focused on measuring many proteins and those that focused on a specific biological process · People increasingly using multiomics to wholistically understanding biology as opposed to a means of comparing the different omes · A shift to researchers using multiple proteomics platforms 11:44 – The rising prominence of proteoforms at US HUPO 15:50 – The future of proteomics as informed by US HUPO 18:06 – What Parag and Andreas hope to see at the next US HUPO 19:57 - Outro | |||
| 22 May 2024 | Why the Dogma around Biology's Central Dogma Is Wrong | 00:17:37 | |
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 | |||
| 19 Jun 2024 | Harnessing Proteoforms to Understand Life's Complexity | 00:24:34 | |
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 | |||