Slavov Laboratory

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Slavov Laboratory

Slavov Laboratory

@slavovLab

We seek principles in the coordination among protein synthesis, metabolism, cell growth and differentiation PI: @slavov_n Videos: https://t.co/Ku19DCIXvX

Boston, MA Katılım Temmuz 2020
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Slavov Laboratory
Slavov Laboratory@slavovLab·
We report many proteins not predicted by the genetic code. They are stable & abundant O( 10³ ) copies / cell. Generative mechanisms include codon-anticodon mismatches & RNA modifications. Their abundance depends on codon frequency & protein stability. biorxiv.org/content/10.110…
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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
Some proteins covary with the cell division cycle similarly across cell types. Others covary in a cell type-dependent way. What is your interpretation ? doi.org/10.1186/s13059…
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Slavov Laboratory
Slavov Laboratory@slavovLab·
A gene may template many dozens of products. Its products can have diverse, even opposing functions. Ascribing the functions of the products to the gene is a simplistic approximation that has outlived its usefulness.
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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
A deeper dive into the article we published last week in @Nature. I will start with the framing and methodology as they are key to understanding the surprising results: Proteomics experiments usually begin with an assumption. nature.com/articles/s4158… 1/
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D. Allan Drummond
D. Allan Drummond@dallandrummond·
Major, major kudos to @slavov_n and team for this breakthrough! We tried to do this many years ago, and failed -- it's stupendously challenging. Brings a huge number of new (and old) questions onto the table!
Prof. Nikolai Slavov@slavov_n

Since the 1960s, the genetic code has been used to predict protein sequences from DNA and mRNA sequences.  Our @Nature article demonstrates that these predictions miss thousands of protein sequences present in human tissues. Across >1,000 human samples, we identified numerous abundant proteins whose amino acid sequences differ from those predicted by the genetic code. These proteins are not rare translation byproducts. They accumulate to thousands of copies per cell. Some are more abundant than the proteins predicted by the genetic code from the same transcripts. Their abundance reflects a combination of alternate RNA decoding mechanisms — including codon-anticodon mismatches, tRNA abundance, and RNA modifications — and selective stabilization of the resulting proteins. The last factor – protein stability – emerges as a major determinant of protein abundance across proteins, proteoforms and cell types: #Proteostasis" target="_blank" rel="nofollow noopener">slavovlab.net/research.htm#P… Alternate RNA decoding is pervasive across functional groups of proteins, healthy and diseased tissues. It affects proteins playing key roles in neurodegeneration, and some alternately decoded proteins show strong enrichment in tumors compared to their surrounding tissues. This discovery has been a long and exhilarating journey with Shira Tsour and the @slavovLab team. It started in 2019 and proceeded through many challenges and thrilling highs. A journey that has opened new perspectives that we long to explore! 1/

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Akos Nyerges
Akos Nyerges@AkosNyerges·
Fascinating work, @slavov_n @slavovLab! +1 factor to keep in mind while designing new genomes and genetic codes, beyond the de novo recoding-induced and alternative ORFs we and others recently reported.
Prof. Nikolai Slavov@slavov_n

Since the 1960s, the genetic code has been used to predict protein sequences from DNA and mRNA sequences.  Our @Nature article demonstrates that these predictions miss thousands of protein sequences present in human tissues. Across >1,000 human samples, we identified numerous abundant proteins whose amino acid sequences differ from those predicted by the genetic code. These proteins are not rare translation byproducts. They accumulate to thousands of copies per cell. Some are more abundant than the proteins predicted by the genetic code from the same transcripts. Their abundance reflects a combination of alternate RNA decoding mechanisms — including codon-anticodon mismatches, tRNA abundance, and RNA modifications — and selective stabilization of the resulting proteins. The last factor – protein stability – emerges as a major determinant of protein abundance across proteins, proteoforms and cell types: #Proteostasis" target="_blank" rel="nofollow noopener">slavovlab.net/research.htm#P… Alternate RNA decoding is pervasive across functional groups of proteins, healthy and diseased tissues. It affects proteins playing key roles in neurodegeneration, and some alternately decoded proteins show strong enrichment in tumors compared to their surrounding tissues. This discovery has been a long and exhilarating journey with Shira Tsour and the @slavovLab team. It started in 2019 and proceeded through many challenges and thrilling highs. A journey that has opened new perspectives that we long to explore! 1/

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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
Since the 1960s, the genetic code has been used to predict protein sequences from DNA and mRNA sequences.  Our @Nature article demonstrates that these predictions miss thousands of protein sequences present in human tissues. Across >1,000 human samples, we identified numerous abundant proteins whose amino acid sequences differ from those predicted by the genetic code. These proteins are not rare translation byproducts. They accumulate to thousands of copies per cell. Some are more abundant than the proteins predicted by the genetic code from the same transcripts. Their abundance reflects a combination of alternate RNA decoding mechanisms — including codon-anticodon mismatches, tRNA abundance, and RNA modifications — and selective stabilization of the resulting proteins. The last factor – protein stability – emerges as a major determinant of protein abundance across proteins, proteoforms and cell types: #Proteostasis" target="_blank" rel="nofollow noopener">slavovlab.net/research.htm#P… Alternate RNA decoding is pervasive across functional groups of proteins, healthy and diseased tissues. It affects proteins playing key roles in neurodegeneration, and some alternately decoded proteins show strong enrichment in tumors compared to their surrounding tissues. This discovery has been a long and exhilarating journey with Shira Tsour and the @slavovLab team. It started in 2019 and proceeded through many challenges and thrilling highs. A journey that has opened new perspectives that we long to explore! 1/
Prof. Nikolai Slavov tweet media
Slavov Laboratory@slavovLab

We report many proteins not predicted by the genetic code. They are stable & abundant O( 10³ ) copies / cell. Generative mechanisms include codon-anticodon mismatches & RNA modifications. Their abundance depends on codon frequency & protein stability. biorxiv.org/content/10.110…

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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
If aging is associated with molecular damage, why don't offspring inherit the accumulated damage of their parents? How does the germline avoid transmitting damage from one generation to the next ? These questions motivated a causal investigation of aging mechanisms: The answer involves a rejuvenation program. As fertilization approaches, sperm-derived signals activate lysosomal acidification in oocytes, triggering the clearance of protein aggregates and restoring proteostasis before the next generation begins. This work suggests that maintaining a youthful proteome is one of the mechanisms that enables biological rejuvenation: >  Proteostasis renewal is a core mechanism by which biological age is reset. Like most good studies, this one also raises many questions about the generality of this observation beyond the studied model systems and the molecular mechanisms by which protein damage is cleared: ⬛ Excitingly, these questions can now be investigated using direct measurements of protein synthesis, degradation, modifications, interactions, and accumulation. Such investigations demand technologies for scalable and direct protein analysis at high-resolution !
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Slavov Laboratory
Slavov Laboratory@slavovLab·
@slavov_n A strong postdoc provides a rare opportunity to develop these skills while working closely with established scientific leaders and while still having the freedom to take intellectual risks.
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Slavov Laboratory
Slavov Laboratory@slavovLab·
@slavov_n Leadership in science is learned by identifying important questions, setting a research vision, managing uncertainty, mentoring junior researchers, building collaborations, securing resources, communicating ideas, and taking responsibility for ambitious projects.
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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
Multiple analyses evaluate postdoctoral positions in financial terms. But discussions focused narrowly on average earnings are incomplete and potentially misleading. Salary is easy to quantify, especially in the shorter term, but it's not the only relevant metric: Not everything that can be counted counts, and not everything that counts can be easily counted. The postdoctoral population spans an extraordinarily broad distribution. For a fraction of postdocs, the position has evolved into something closer to a research assistant role than the advanced training position it was originally intended to be. For those researchers, analyses showing lower lifetime earnings and delayed career progression may accurately reflect tradeoffs. But that is not the whole story. For postdoctoral fellows who are training to become scientific leaders -- future principal investigators, research directors, founders, and builders of new fields -- the postdoc can be a uniquely valuable phase of accelerated growth. It is an opportunity to develop independence, leadership, judgment, vision, and the ability to create entirely new research directions. The impact of that experience is difficult to capture in salary statistics. The evolution of the postdoctoral system reflects many forces: the expansion of the research enterprise, funding structures, institutional incentives, and broader changes in higher education. These changes have undoubtedly made postdoctoral positions less attractive for many researchers. For an elite group of capable, ambitious, and highly motivated scientists, a great postdoc remains one of the most powerful career accelerators available. The challenge is not whether postdocs should exist. The challenge is ensuring that more postdoctoral positions truly function as training for scientific leadership rather than simply as additional labor.
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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
We have studied proteins and proteomes for decades. Yet, our studies and methods have been rather limited to hypothesis testing. As a result, the proteome remains a frontier that awaits to be investigated with discovery-driven methods. nikolai.slavovlab.net/Proteome-secre…
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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
Boston is an amazing city for science, but it's an expensive place to visit. To help make SCP2026 more affordable and accessible, we've secured conference housing for $115 / night. We hope this enables broader participation from students, trainees, and researchers around the world.
Prof. Nikolai Slavov tweet media
Single-Cell Proteomics Conference@SCP_meeting

The program for #SCP2026 is online. The talks span diverse technologies and biological questions. Join the discussions, flash talks, and hands-on workshop. 🗓️ July 14-16, 2026 | Boston, USA 🔗 Check out the full program: single-cell.net/proteomics/scp…

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Prof. Nikolai Slavov
Prof. Nikolai Slavov@slavov_n·
Mass spectrometry proteomics loves benchmarks. But I have not seen an important one: - Accuracy of proteome quantification when using short LC gradients. timsTOF and Orbitrap Astral instruments allow quantifying 7 - 9k proteins from 200ng samples using very short short separation times affording the analysis of 200 – 500 samples / day. ⬛ Have you seen accuracy benchmarks for this workflow ?
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