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Article ; Online: The flagellar germ-line hypothesis: How flagellate and ciliate gametes significantly shaped the evolution of organismal complexity.

Lindemann, Charles B

BioEssays : news and reviews in molecular, cellular and developmental biology

2021 Volume 44, Issue 3, Page(s) e2100143

Abstract: This essay presents a hypothesis which contends that the development of organismic complexity in the eukaryotes depended extensively on propagation via flagellated and ciliated gametes. Organisms utilizing flagellate and ciliate gametes to propagate ... ...

Abstract	This essay presents a hypothesis which contends that the development of organismic complexity in the eukaryotes depended extensively on propagation via flagellated and ciliated gametes. Organisms utilizing flagellate and ciliate gametes to propagate their germ line have contributed most of the organismic complexity found in the higher animals. The genes of the flagellum and the flagellar assembly system (intraflagellar transport) have played a disproportionately important role in the construction of complex tissues and organs. The hypothesis also proposes that competition between large numbers of haploid flagellated male gametes rigorously conserved the functionality of a key set of flagellar genes for more than 700 million years. This in turn has insured that a large set (>600) of highly functional cytoskeletal and signal pathway genes is always present in the lineage of organisms with flagellated or ciliated gametes to act as a dependable resource, or "toolkit," for organ elaboration. Also see the video abstract here: https://youtu.be/lC5nC-WOcm8.
MeSH term(s)	Animals ; Biological Transport ; Flagella/genetics ; Flagella/metabolism ; Germ Cells ; Male
Language	English
Publishing date	2021-12-29
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.202100143
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Article: The flagellar germ‐line hypothesis: How flagellate and ciliate gametes significantly shaped the evolution of organismal complexity

Lindemann, Charles B.

BioEssays. 2022 Mar., v. 44, no. 3

2022

Abstract	This essay presents a hypothesis which contends that the development of organismic complexity in the eukaryotes depended extensively on propagation via flagellated and ciliated gametes. Organisms utilizing flagellate and ciliate gametes to propagate their germ line have contributed most of the organismic complexity found in the higher animals. The genes of the flagellum and the flagellar assembly system (intraflagellar transport) have played a disproportionately important role in the construction of complex tissues and organs. The hypothesis also proposes that competition between large numbers of haploid flagellated male gametes rigorously conserved the functionality of a key set of flagellar genes for more than 700 million years. This in turn has insured that a large set (>600) of highly functional cytoskeletal and signal pathway genes is always present in the lineage of organisms with flagellated or ciliated gametes to act as a dependable resource, or “toolkit,” for organ elaboration. Also see the video abstract here: https://youtu.be/lC5nC-WOcm8
Keywords	cytoskeleton ; eukaryotic cells ; evolution ; flagellum ; germ cells ; haploidy ; males ; signal transduction
Language	English
Dates of publication	2022-03
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	50140-2
ISSN	1521-1878 ; 0265-9247
ISSN (online)	1521-1878
ISSN	0265-9247
DOI	10.1002/bies.202100143
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Article ; Online: The many modes of flagellar and ciliary beating: Insights from a physical analysis.

Lindemann, Charles B / Lesich, Kathleen A

Cytoskeleton (Hoboken, N.J.)

2021 Volume 78, Issue 2, Page(s) 36–51

Abstract: The mechanism that allows the axoneme of eukaryotic cilia and flagella to produce both helical and planar beating is an enduring puzzle. The nine outer doublets of eukaryotic cilia and flagella are arranged in a circle. Therefore, each doublet pair with ... ...

Abstract	The mechanism that allows the axoneme of eukaryotic cilia and flagella to produce both helical and planar beating is an enduring puzzle. The nine outer doublets of eukaryotic cilia and flagella are arranged in a circle. Therefore, each doublet pair with its associated dynein motors, should produce torque to bend the flagellum in a different direction. Sequential activation of each doublet pair should, therefore result in a helical bending wave. In reality, most cilia and flagella have a well-defined bending plane and many exhibit an almost perfectly flat (planar) beating pattern. In this analysis we examine the physics that governs flagellar bending, and arrive at two distinct possibilities that could explain the mechanism of planar beating. Of these, the mechanism with the best observational support is that the flagellum behaves as two ribbons of doublets interacting with a central partition. We also examine the physics of torsion in flagella and conclude that torsion could play a role in transitioning from a planar to a helical beating modality in long flagella. Lastly, we suggest some tests that would provide theoretical and/or experimental evaluation of our proposals.
MeSH term(s)	Axoneme/metabolism ; Cilia/metabolism ; Cytoskeleton/metabolism ; Dyneins/metabolism ; Flagella/metabolism
Chemical Substances	Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2021-03-15
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2534372-5
ISSN	1949-3592 ; 1949-3584
ISSN (online)	1949-3592
ISSN	1949-3584
DOI	10.1002/cm.21656
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Article ; Online: Engaging the "clutch" to move forward.

Lindemann, Charles B

Biophysical journal

2014 Volume 107, Issue 7, Page(s) 1487–1488

MeSH term(s)	Flagella/metabolism ; Models, Biological ; Movement
Language	English
Publishing date	2014-10-08
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2014.07.065
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Article ; Online: Dynein regulation: going into circles can set things straight.

Lindemann, Charles B

Biophysical journal

2014 Volume 106, Issue 11, Page(s) 2285–2287

MeSH term(s)	Axonemal Dyneins/chemistry ; Axoneme/metabolism ; Chlamydomonas reinhardtii/metabolism ; Models, Biological
Chemical Substances	Axonemal Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2014-06-04
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2014.04.003
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Article ; Online: Experimental evidence for the geometric clutch hypothesis.

Lindemann, Charles B

Current topics in developmental biology

2011 Volume 95, Page(s) 1–31

Abstract: The cilia and flagella of eukaryotic cells are complex filamentous organelles that undulate rapidly and produce propulsive force against the fluids that surround the living cell. They provide a number of important functions in the life cycle of higher ... ...

Abstract	The cilia and flagella of eukaryotic cells are complex filamentous organelles that undulate rapidly and produce propulsive force against the fluids that surround the living cell. They provide a number of important functions in the life cycle of higher organisms including humans. A flagellum propels the spermatozoa to the site of fertilization and cilia move the egg through the oviduct to the uterus and have a role in left-right asymmetry in the developing embryo and contribute to normal brain morphology. The geometric clutch hypothesis is a mechanistic explanation of how the repetitive bending of cilia and flagella is generated. This chapter recounts the events leading to the development of the geometric clutch hypothesis, explores the conceptual framework of the hypothesis as it relates to properties of the axoneme, and considers the experimental support for the existence of such a mechanism in real cilia and flagella.
MeSH term(s)	Axoneme/physiology ; Biomechanical Phenomena ; Cilia/physiology ; Dyneins/metabolism ; Flagella/physiology ; Models, Biological
Chemical Substances	Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2011
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1557-8933 ; 0070-2153
ISSN (online)	1557-8933
ISSN	0070-2153
DOI	10.1016/B978-0-12-385065-2.00001-3
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Article ; Online: Functional anatomy of the mammalian sperm flagellum.

Lindemann, Charles B / Lesich, Kathleen A

Cytoskeleton (Hoboken, N.J.)

2016 Volume 73, Issue 11, Page(s) 652–669

Abstract: The eukaryotic flagellum is the organelle responsible for the propulsion of the male gamete in most animals. Without exception, sperm of all mammalian species use a flagellum for swimming. The mammalian sperm has a centrally located 9 + 2 arrangement of ... ...

Abstract	The eukaryotic flagellum is the organelle responsible for the propulsion of the male gamete in most animals. Without exception, sperm of all mammalian species use a flagellum for swimming. The mammalian sperm has a centrally located 9 + 2 arrangement of microtubule doublets and hundreds of accessory proteins that together constitute an axoneme. However, they also possess several characteristic peri-axonemal structures that make the mammalian sperm tail function differently. These modifications include nine outer dense fibers (ODFs) that are paired with the nine outer microtubule doublets of the axoneme, and are anchored in a structure called the connecting piece located at the base. The presence of the ODFs and connecting piece, and the absence of a basal body, dictate that physical forces generated by the dynein motors are transmitted to the base of the flagellum through the ODFs. Mammalian sperm flagella also possess a mitochondrial and a fibrous sheath that encircle most of the axoneme. These sheaths and the ODFs add mechanical rigidity to the flagellum creating the functional effect of increasing bend wavelength, which requires the entrainment of more dynein motors in the production of a single wave. The sheaths also act as a retinaculum and maintain the integrity of the central axoneme when large bending torques are generated by dynein. Large torque production is crucial to the process of hyperactivation and the unique motility transitions associated with effective fertilizing capacity. Consequently, these specialized anatomical features are essential for the effective interaction of sperm with the female reproductive tract and ovum. © 2016 Wiley Periodicals, Inc.
Language	English
Publishing date	2016-11
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	2534372-5
ISSN	1949-3592 ; 1949-3584
ISSN (online)	1949-3592
ISSN	1949-3584
DOI	10.1002/cm.21338
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Article ; Online: Heart of the beat (the flagellar beat, that is).

Lindemann, Charles B

Biophysical journal

2009 Volume 97, Issue 11, Page(s) 2865–2866

MeSH term(s)	Axoneme/metabolism ; Cilia/metabolism ; Dyneins/metabolism ; Flagella/metabolism ; Models, Biological
Chemical Substances	Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2009-02-01
Publishing country	United States
Document type	Comment ; Journal Article
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2009.09.059
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Article ; Online: The geometric clutch at 20: stripping gears or gaining traction?

Lindemann, Charles B / Lesich, Kathleen A

Reproduction (Cambridge, England)

2015 Volume 150, Issue 2, Page(s) R45–53

Abstract: ... that remain attached to the B-subtubule of the adjacent doublet. ...

Abstract	It has been 20 years since the geometric clutch (GC) hypothesis was first proposed. The core principle of the GC mechanism is fairly simple. When the axoneme of a eukaryotic flagellum is bent, mechanical stress generates forces transverse to the outer doublets (t-forces). These t-forces can push doublets closer together or pry them apart. The GC hypothesis asserts that changes in the inter-doublet spacing caused by t-forces are responsible for the activation and deactivation of the dynein motors, that creates the beat cycle. A series of computer models utilizing the clutch mechanism has shown that it can simulate ciliary and flagellar beating. The objective of the present review is to assess where things stand with the GC hypothesis in the clarifying light of new information. There is considerable new evidence to support the hypothesis. However, it is also clear that it is necessary to modify some of the original conceptions of the hypothesis so that it can be consistent with the results of recent experimental and ultrastructural studies. In particular, dynein deactivation by t-forces must be able to occur with dyneins that remain attached to the B-subtubule of the adjacent doublet.
MeSH term(s)	Animals ; Cilia/genetics ; Cilia/physiology ; Computer Simulation ; Dyneins/genetics ; Dyneins/physiology ; Flagella/genetics ; Flagella/physiology ; Humans ; Male ; Mutation/physiology ; Protein Conformation ; Spermatozoa/physiology
Chemical Substances	Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2015-08
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2034501-X
ISSN	1741-7899 ; 1470-1626 ; 1476-3990
ISSN (online)	1741-7899
ISSN	1470-1626 ; 1476-3990
DOI	10.1530/REP-14-0498
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Article ; Online: A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease.

Zuiani, Adam / Dulberger, Charles L / De Silva, Nilushi S / Marquette, Meghan / Lu, Yu-Jung / Palowitch, Gavin M / Dokic, Anja / Sanchez-Velazquez, Ricardo / Schlatterer, Katja / Sarkar, Sanjay / Kar, Swagata / Chawla, Bhavna / Galeev, Alibek / Lindemann, Claudia / Rothenberg, Daniel A / Diao, Huitian / Walls, Alexandra C / Addona, Theresa A / Mensa, Federico /

Vogel, Annette B / Stuart, Lynda M / van der Most, Robbert / Srouji, John R / Türeci, Özlem / Gaynor, Richard B / Şahin, Uğur / Poran, Asaf

Cell

2024 Volume 187, Issue 6, Page(s) 1363–1373.e12

Abstract: In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and ... ...

Abstract	In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).
MeSH term(s)	Animals ; Humans ; Mice ; Macaca fascicularis ; Monkeypox virus/genetics ; Mpox (monkeypox)/immunology ; Mpox (monkeypox)/prevention & control ; Smallpox Vaccine ; Vaccines, Combined ; Vaccinia virus/genetics
Chemical Substances	Smallpox Vaccine ; Vaccines, Combined
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2024.01.017
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