Integrated multi-omics analysis of chemical signaling in wild rodents

• Název práce v češtině: Integrovaná multi-omics analýza chemické signalizace u divokých hlodavců
• Název v anglickém jazyce: Integrated multi-omics analysis of chemical signaling in wild rodents
• Klíčová slova: proteomika, myš domácí, mikrobiom
• Klíčová slova anglicky: proteomics, house mouse, microbiome
• Akademický rok vypsání: 2018/2019
• Typ práce: disertační práce
• Jazyk práce: angličtina
• Ústav: Katedra zoologie (31-170)
• Vedoucí / školitel: prof. Mgr. Pavel Stopka, Ph.D.
• Řešitel: Mgr. Tereza Matějková, Ph.D. - zadáno a potvrzeno stud. odd.
• Datum přihlášení: 03.10.2018
• Datum zadání: 10.10.2018
• Datum potvrzení stud. oddělením: 10.10.2018
• Datum odevzdání elektronické podoby: 22.12.2022
• Datum proběhlé obhajoby: 08.03.2023
• Oponenti: prof. RNDr. Miloš Macholán, CSc.
• Konzultanti: Mgr. Romana Stopková, Ph.D.

Zásady pro vypracování

Proteomika
Proteomické praktikum
Computational genomics

Seznam odborné literatury

Augustin, Schröder, Murillo Rincón, Fraune, Anton-Erxleben, Herbst, Wittlieb,
Schwentner, Grötzinger, Wassenaar, and Bosch. 2017. “A Secreted Antibacterial
Neuropeptide Shapes the Microbiome of Hydra.” Nature Communications 8 (1): 698.
Bravo, Forsythe, Chew, Escaravage, Savignac, Dinan, Bienenstock, and Cryan. 2011.
“Ingestion of Lactobacillus Strain Regulates Emotional Behavior and Central GABA
Receptor Expression in a Mouse via the Vagus Nerve.” Proceedings of the National
Academy of Sciences of the United States of America 108 (38): 16050–55.
Černá, Kuntová, Talacko, Stopková, and Stopka. 2017. “Differential Regulation of Vaginal
Lipocalins (OBP, MUP) during the Estrous Cycle of the House Mouse.” Scientific Reports 7
(1): 11674.
Eckburg, Bik, Bernstein, Purdom, Dethlefsen, Sargent, Gill, Nelson, and Relman. 2005.
“Diversity of the Human Intestinal Microbial Flora.” Science (New York, N.Y.) 308 (5728):
1635–38.
Fellows, Denizot, Stellato, Cuomo, Jain, Stoyanova, Balázsi, … Varga-Weisz. 2018.
“Microbiota Derived Short Chain Fatty Acids Promote Histone Crotonylation in the Colon
through Histone Deacetylases.” Nature Communications 9 (1): 105.
Janotova, and Stopka. 2011. “The Level of Major Urinary Proteins Is Socially Regulated in
Wild Mus Musculus Musculus.” Journal of Chemical Ecology 37 (6): 647–56.
Kuntová, Stopková, and Stopka. 2018. “Transcriptomic and Proteomic Profiling Revealed
High Proportions of Odorant Binding and Antimicrobial Defense Proteins in Olfactory
Tissues of the House Mouse.” Frontiers in Genetics 9: 26.
McDermott. 2013. “Antimicrobial Compounds in Tears.” Experimental Eye Research 117
(December): 53–61.
Nagel, Bansal, Stopka, … 2018. “A systematic comparison of semiochemical signaling in the
accessory olfactory system of wild and lab strain mice.“ Chemical Senses 43: E31-E31.
Stopka, Janotova, and Heyrovsky. 2007. “The Advertisement Role of Major Urinary Proteins
in Mice.” Physiology & Behavior 91 (5): 667–70.

Předběžná náplň práce

Each surface of an animal which is in touch with surrounding environment has to deal with
ubiquitous bacteria. In mammals, these surfaces include eyes, nose, oral cavity which proceeds
into gastrointestinal tract, utero-vaginal environment, etc.. While some surfaces have evolved
to become a bacteria-hostile environment with multiple antimicrobial features (i. e. eyes,
(McDermott 2013)), others create a bacterial-friendly environment leading to an
establishment of a complex net of host-microbe interactions which are essential for the health
of the host (i.e. microbiom in gastrointestinal tract (Eckburg et al. 2005)).
There is rising evidence that the presence of bacteria on the other surfaces (nose or
utero-vaginal environment) is used in chemical communication among individuals. During
ovulation the utero-vaginal environment is overpopulated by bacteria. It was proved that in
the same time there are antimicrobial proteins which regulate populations of bacteria, and
also lipocalins (Major-urinary and Odorant-binding Proteins) which transport volatile organic
compounds out of the body (Černá et al. 2017). These compounds serve as chemical signals
which reveal information on the female reproductive state to males. Males similarly stimulate
females with their up-regulated chemical signals which are present in the urine and are also
carried out by Major-urinary Proteins (Janotova et al. 2011; Stopka et al. 2007). Moreover,
lipocalins (Major-urinary and Odorant-binding Proteins) are also present in olfactory tissues
of the nose where they serve removing organic compounds from defeated bacteria to
detoxify mucosal tissues and also serve removing various background odour compounds for a
proper functioning of the mouse sensory epithelia (Kuntová et al. 2018). The inbred and wild
mice have different signals (due to the presence of bacteria in wild mice), thus they are
differently stimulated in the brain (Nagel et al. 2018). Furthermore, there is increasing
evidence that symbiotic bacteria are behind many physiological processes not only in
mammals but also in animals with a lower complexity such as Hydra spp. (Augustin et al.
2017). Lipocalins and antimicrobial proteins have co-ordinated expressions to control for
bacterial growth (Kuntová et al. 2018).
We plan to study the proteomic variation in wild-derived mouse during its estrouscycle
and in the two systems of tissues and their secretions (i. e. utero-vaginal environment
and oro-facial tissues and secretions including tears, nasal secretion and saliva), as previous
studies have revealed high abundances of bacteria and high abundances of the host
antimicrobial peptides in these tissues (Černá et al. 2017; Kuntová et al. 2018). Thus, these
two systems are amenable to study interactions between symbiotic microbiota and the host.
Recent studies/papers published during last five years have revealed that microbiota
significantly influences fundamental physiological processes such as digestion, immunity,
communication between organs along the gut-brain axis (Fellows et al. 2018; Bravo et al.
2011), estrous cycles, individual growth and protection against other pathogens and cancer
cells. However, precise mechanisms of the regulation of the microbiota are not well known.
This project aims to introduce a new mouse model, which was generated in Pavel Stopka's lab,
to uncover the basis of communication, cooperation and the maintenance of symbiosis
between bacterial and the host cells and tissues.

Předběžná náplň práce v anglickém jazyce

Each surface of an animal which is in touch with surrounding environment has to deal with
ubiquitous bacteria. In mammals, these surfaces include eyes, nose, oral cavity which proceeds
into gastrointestinal tract, utero-vaginal environment, etc.. While some surfaces have evolved
to become a bacteria-hostile environment with multiple antimicrobial features (i. e. eyes,
(McDermott 2013)), others create a bacterial-friendly environment leading to an
establishment of a complex net of host-microbe interactions which are essential for the health
of the host (i.e. microbiom in gastrointestinal tract (Eckburg et al. 2005)).
There is rising evidence that the presence of bacteria on the other surfaces (nose or
utero-vaginal environment) is used in chemical communication among individuals. During
ovulation the utero-vaginal environment is overpopulated by bacteria. It was proved that in
the same time there are antimicrobial proteins which regulate populations of bacteria, and
also lipocalins (Major-urinary and Odorant-binding Proteins) which transport volatile organic
compounds out of the body (Černá et al. 2017). These compounds serve as chemical signals
which reveal information on the female reproductive state to males. Males similarly stimulate
females with their up-regulated chemical signals which are present in the urine and are also
carried out by Major-urinary Proteins (Janotova et al. 2011; Stopka et al. 2007). Moreover,
lipocalins (Major-urinary and Odorant-binding Proteins) are also present in olfactory tissues
of the nose where they serve removing organic compounds from defeated bacteria to
detoxify mucosal tissues and also serve removing various background odour compounds for a
proper functioning of the mouse sensory epithelia (Kuntová et al. 2018). The inbred and wild
mice have different signals (due to the presence of bacteria in wild mice), thus they are
differently stimulated in the brain (Nagel et al. 2018). Furthermore, there is increasing
evidence that symbiotic bacteria are behind many physiological processes not only in
mammals but also in animals with a lower complexity such as Hydra spp. (Augustin et al.
2017). Lipocalins and antimicrobial proteins have co-ordinated expressions to control for
bacterial growth (Kuntová et al. 2018).
We plan to study the proteomic variation in wild-derived mouse during its estrouscycle
and in the two systems of tissues and their secretions (i. e. utero-vaginal environment
and oro-facial tissues and secretions including tears, nasal secretion and saliva), as previous
studies have revealed high abundances of bacteria and high abundances of the host
antimicrobial peptides in these tissues (Černá et al. 2017; Kuntová et al. 2018). Thus, these
two systems are amenable to study interactions between symbiotic microbiota and the host.
Recent studies/papers published during last five years have revealed that microbiota
significantly influences fundamental physiological processes such as digestion, immunity,
communication between organs along the gut-brain axis (Fellows et al. 2018; Bravo et al.
2011), estrous cycles, individual growth and protection against other pathogens and cancer
cells. However, precise mechanisms of the regulation of the microbiota are not well known.
This project aims to introduce a new mouse model, which was generated in Pavel Stopka's lab,
to uncover the basis of communication, cooperation and the maintenance of symbiosis
between bacterial and the host cells and tissues.