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Mohamed ElTanbouly Profile picture
@Plasmacellguy
Sep 9, 2021 • 21 tweets • 21 min read • Read on X
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Inspired by @philipcball's question, here is a 🧵of some of the most beautiful #biology experiments (in my opinion)

Disclaimer: Not in order and no details (links provided)
1-Messelson-Stahl discovery of semi-conservative DNA replication (Okay that's obvious but bear with me)

Year: 1958

Side-note: notice how humble the paper title is.

Paper ➡️pnas.org/content/44/7/6…

Summaries ➡️
➡️
2-Hershey-Chase:

Viruses replicate by way of their nucleic acids (not proteins)

DNA is the origin of hereditary material

Year: 1952

Paper ➡️ rupress.org/jgp/article-pd…

Summary ➡️
3- Isolation of messenger RNA
Brenner, Jacob, Watson and colleagues

Papers ➡️ nature.com/articles/19057…
➡️nature.com/articles/19058…

Summary ➡️ bit.ly/CSHLsum

Brenner's story ➡️ bit.ly/BrennerYT
➡️bit.ly/Biochapter12
4- #Immunology (1)

Karl Landsteiner shows that antibodies can be generated against literally anything (with a lot of mechanistic analysis)

Year: 1937

➡️ amazon.com/dp/B00MAVFQ2Y?…
5- #Immunology (2)

Affinity maturation: antibody affinity increases over the course of an immune response

Herman Eisen & Siskin

Simply elegant.

Year: 1964
6- Luria-Delbrück fluctuation analysis:

"The mutational event precedes the selective pressure used to reveal it."

Year: 1943

Paper ➡️ bit.ly/LuriaDelbrück

Summary ➡️
7- Hayflick limit:

Year: 1961

Normal cells have limited capacity to divide (40 to 60 times)

Paper ➡️ bit.ly/Hayflicklimit

Summary from Hayflick ➡️
(Term coined by Frank Burnet)
8- Induction of pluripotency:

S. Yamanaka and co. (The Yamanaka factors)
4 factors make cells younger

Year: 2006

Paper ➡️ cell.com/cell/fulltext/…

Nobel lecture ➡️ nobelprize.org/prizes/medicin…
9- #Immunology (3)
Induction of acquired immune tolerance

Medawar and colleagues: a SINGLE experiment that changed immunology

Year: 1953

Paper ➡️ nature.com/articles/17260…

Nobel lecture ➡️ nobelprize.org/prizes/medicin…

Interesting slightly relevant ➡️
10- Protein Secretory pathway: Pulse-chase experiment

George Palade and colleagues Siekevitz and Jamieson

Year: 1967

Paper ➡️ doi.org/10.1083/jcb.34…

Really nice summary ➡️ molbiolcell.org/doi/10.1091/mb…

Modified from images by James Jamieson
11- Transposons: Jumping genes

Barbara McClintock

Year: 1950

Paper ➡️ pnas.org/content/36/6/3…

Nobel lecture ➡️ nobelprize.org/prizes/medicin…

Summary ➡️
12- #Immunology (4): Inducible switching of antigen receptor specificity

Klaus Rajewsky and co.

Year: 2000
(also repeated in 2019 for a different question)

Paper ➡️ nature.com/articles/35036…
13- #Immunology (5) Discovery and imaging of meningeal Lymphatics

Kipnis and colleagues

Year: 2015

Paper ➡️ nature.com/articles/natur…

(Side-note: proposed by Paolo Mascagni 200 years ago)
14- #Immunology (6) Epigenetics (not gene expression) clearly distinguish memory and naive T cells

Love the heavy water multi-year tracking of T cells.

R. Akondy and Rafi Ahmed

Year: 2017

Paper ➡️ nature.com/articles/natur…

Lecture ➡️ videocast.nih.gov/watch=23509
15- #Immunology (7)

Discovery of mammalian Pattern Recognition pathway

Medzhitov & Janeway

Year: 1997

Paper ➡️ nature.com/articles/41131

Conceptualization ➡️
16- #Immunology (8)

Visualizing clonal burst and dominance in the germinal center

Victora and colleagues

Year: 2016

Paper ➡️ science.org/doi/full/10.11…
17- #Immunology (9)

Two tolerance checkpoints during B cell development

Hedda Wardemann & M. C. Nussenzweig

Year: 2003
18- #Immunology (10)

Some plasma cells live long. Labeling of plasma cells. Tracking of antibody

M Slifka & R. Ahmed (1998)
Manz & Radbruch (1997)
Amanna & Slifka (2010)

Papers ➡️ bit.ly/Slifka1998
nature.com/articles/40540
nejm.org/doi/full/10.10…
19- RNA ➡️ DNA

Reverse transcription: enzyme activity and inhibition assays

David Baltimore & Howard Temin (& Satoshi Mizutani)

Year: 1970

Papers: nature.com/articles/22612…
nature.com/articles/22612…

Conceptualization ➡️ nature.com/articles/22756…
20- Chemical synthesis of a virus

Eckard Wimmer and colleagues describe the synthesis of poliovirus in vitro (cell-free system)

Year: 2002

Paper ➡️ science.org/doi/abs/10.112…

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More from @Plasmacellguy

Mohamed ElTanbouly Profile picture
Nov 10, 2023
1/Where do I start?

Is it at Von Behring and Kitasato who were the first to discover that immunization of animals with diptheria and tetanus toxins resulted in soluble substances in the serum that neutralize these same toxins making them harmless?
bit.ly/VonBehring1890

From "The generative grammar of the immune system" by Niels K Jerne (EMBO, 1985) PMID: 2410261 Also see his Nobel lecture of the same title.
2/Which later led to a big development in anti-sera therapeutics against multiple diseases

e.g. J. Bordet's work on cholera

(nicely summarized here )bit.ly/Bordet1895
bit.ly/Bordetsummary
3/Later, it became clear that these "substances" (antibodies) are proteins and are made up of γ-globulins


And 8 years after, it was known that these antibodies are made by plasma cells

(microscopy) bit.ly/TiseliusKabat1…
bit.ly/Fagraeus1947
bit.ly/Coons1955

PMID: 19870831 10.1084/jem.69.1.119 Serum protein separation shows that antibodies are γ-globulins
PMID: 18897986 https://www.nature.com/articles/159499a0
Read 25 tweets
Mohamed ElTanbouly Profile picture
Mar 29, 2023
(1) The plasma cell (PC) field has been booming and blooming in the past two years

Some dogmas and notions were quietly taken apart

An #immunology 🧵
(2) First, a pervasive dogma was that germinal centers are the sole origin of long-lived PCs

There is accumulating evidence that LLPCs can originate from T-cell-independent (extrafollicular) responses

bit.ly/Fidler1975
bit.ly/Bortnik2012
bit.ly/Bortnik2013 Figure 1 from PMID: 22529295
(3) Even within a GC-derived response, if you genetically label PCs prior to GC formation, you still get Long-lived plasma cells during this nascent extrafollicular response

bit.ly/Koike2023

Koike et al. here elegantly making use of two "timestamping" genetic tools Figure 4 of PMID: 36515679
Read 17 tweets
Mohamed ElTanbouly Profile picture
Mar 1, 2022
(1) A lot of Immunologists are (justifiably) obsessed with T cell exhaustion.

Very few discuss memory inflation 📈 despite its relevance to #vaccines and #aging

#Immunology #TCELL

Diagram and background info mainly from bit.ly/OHara2012
(2) Inflation: induction of memory [CD8+] T cells that increase in frequency over time to >10% of the entire T cell pool in blood and higher abundance in peripheral tissues (e.g. liver and lung)
(3) First reported (to my knowledge) in a mouse model of CMV (MCMV)

Recall (by contrast) how chronic LCMV (clone 13) induces T cell exhaustion
bit.ly/Holtappels2000
bit.ly/Karrer2003
Read 18 tweets
Mohamed ElTanbouly Profile picture
Jan 25, 2022
1/Truly inspiring and [by far] my favorite talk (so far) @Midwinter_Immun

quick 🧵
2/Kagan and co. address the outstanding question: How can you activate and program a dendritic cell to promote protective (including antitumor) immunity?

Same as, why have DC-based vaccines and all cancer vaccines failed thus far?
3/The key is in keeping the DC alive and active during stimulation.

Most adjuvants (e.g. LPS, alum, polyI:C) induce pyroptosis which (while triggering local inflammation) limits the activity and costimulatory potential of a dendritic cell
Read 17 tweets
Mohamed ElTanbouly Profile picture
Oct 20, 2020
Our review on peripheral T cell tolerance is now online in @NatRevImmunol

Link rdcu.be/b8LRt

I want to state a few relevant points in this 🧵

#Science #Immunology #AcademicTwitter Image
Most studies and perspectives focus on one mechanism of tolerance and few have seriously considered all these together in the context of T cell differentiation.

We attempted to draw a conceptual framework for the known tolerance checkpoints at each stage of the T cell lifespan
In summary, we present 6 main tolerance hallmarks:
Quiescence
Ignorance
Anergy
Exhaustion
Senescence
Death
Read 9 tweets

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