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2. Water in peripheral TM-interfaces of Orai1-channels triggers pore opening

Author

Hopl, Valentina, Tiffner, Adéla, Wutscher, Armin, Sallinger, Matthias, Grabmayr, Herwig, Prantl, Magdalena, Fröhlich, Maximilian, Söllner, Julia, Weiß, Sarah, Najjar, Hadil, Nazarenko, Yuliia, Harant, Selina, Kriško, Natalia, Fahrner, Marc, Humer, Christina, Höglinger, Carmen, Krobath, Heinrich, Bonhenry, Daniel, and Derler, Isabella

Published
2024
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3. Genetic code expansion, an emerging tool in the Ca2+ ion channel field.

Author

Söllner, Julia and Derler, Isabella

Subjects
*AMINO acids, *ION channels, *GENE expression, *GENETIC regulation, *CHEMICAL synthesis
Abstract

Various methods for characterizing binding forces as well as for monitoring and remote control of ion channels are still emerging. A recent innovation is the direct incorporation of unnatural amino acids (UAAs) with corresponding biophysical or biochemical properties, which are integrated using genetic code expansion technology. Minimal changes to natural amino acids, which are achieved by chemical synthesis of corresponding UAAs, are valuable tools to provide insight into the contributions of physicochemical properties of side chains in binding events. To gain unique control over the conformational changes or function of ion channels, a series of light‐sensitive, chemically reactive and posttranslationally modified UAAs have been developed and utilized. Here, we present the existing UAA tools, their mode of action, their potential and limitations as well as their previous applications to Ca2+‐permeable ion channels. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Insights into the dynamics of the Ca2+ releaseactivated Ca2+ channel pore-forming complex Orai1.

Author

Fröhlich, Maximilian, Söllner, Julia, and Derler, Isabella

Subjects
*CALCIUM channels, *GENETIC code, *CELL membranes, *ION channels, *ENDOPLASMIC reticulum, *AMINO acids
Abstract

An important calcium (Ca2+) entry pathway into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel, which controls a series of downstream signaling events such as gene transcription, secretion and proliferation. It is composed of a Ca2+ sensor in the endoplasmic reticulum (ER), the stromal interaction molecule (STIM), and the Ca2+ ion channel Orai in the plasma membrane (PM). Their activation is initiated by receptor-ligand binding at the PM, which triggers a signaling cascade within the cell that ultimately causes store depletion. The decrease in ER-luminal Ca2+ is sensed by STIM1, which undergoes structural rearrangements that lead to coupling with Orai1 and its activation. In this review, we highlight the current understanding of the Orai1 pore opening mechanism. In this context, we also point out the questions that remain unanswered and how these can be addressed by the currently emerging genetic code expansion (GCE) technology. GCE enables the incorporation of non-canonical amino acids with novel properties, such as light-sensitivity, and has the potential to provide novel insights into the structure/function relationship of CRAC channels at a single amino acid level in the living cell. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data

Author

Abdallah, Kald, Aittokallio, Tero, Airola, Antti, Anghe, Catalina, Azima, Helia, Baertsch, Robert, Ballester, Pedro J, Bare, Chris, Bhandari, Vinayak, Bot, Brian M, Dang, Cuong C, Dunbar, Maria Bekker-Nielsen, Buchardt, Ann-Sophie, Buturovic, Ljubomir, Cao, Da, Chalise, Prabhakar, Cho, Junwoo, Chu, Tzu-Ming, Coley, R Yates, Conjeti, Sailesh, Correia, Sara, Costello, James C, Dai, Ziwei, Dai, Junqiang, Dargatz, Philip, Delavarkhan, Sam, Deng, Detian, Dhanik, Ankur, Du, Yu, Elangovan, Aparna, Ellis, Shellie, Elo, Laura L, Espiritu, Shadrielle M, Fan, Fan, Farshi, Ashkan B, Freitas, Ana, Fridley, Brooke, Friend, Stephen, Fuchs, Christiane, Gofer, Eyal, Peddinti, Gopalacharyulu, Graw, Stefan, Greiner, Russ, Guan, Yuanfang, Guinney, Justin, Guo, Jing, Gupta, Pankaj, Guyer, Anna I, Han, Jiawei, Hansen, Niels R, Chang, Billy HW, Hirvonen, Outi, Huang, Barbara, Huang, Chao, Hwang, Jinseub, Ibrahim, Joseph G, Jayaswa, Vivek, Jeon, Jouhyun, Ji, Zhicheng, Juvvadi, Deekshith, Jyrkkiö, Sirkku, Kanigel-Winner, Kimberly, Katouzian, Amin, Kazanov, Marat D, Khan, Suleiman A, Khayyer, Shahin, Kim, Dalho, Golinska, Agnieszka K, Koestler, Devin, Kokowicz, Fernanda, Kondofersky, Ivan, Krautenbacher, Norbert, Krstajic, Damjan, Kumar, Luke, Kurz, Christoph, Kyan, Matthew, Laajala, Teemu D, Laimighofer, Michael, Lee, Eunjee, Lesinski, Wojciech, Li, Miaozhu, Li, Ye, Lian, Qiuyu, Liang, Xiaotao, Lim, Minseong, Lin, Henry, Lin, Xihui, Lu, Jing, Mahmoudian, Mehrad, Manshaei, Roozbeh, Meier, Richard, Miljkovic, Dejan, Mirtti, Tuomas, Mnich, Krzysztof, Navab, Nassir, Neto, Elias C, Newton, Yulia, Norman, Thea, Pahikkala, Tapio, Pal, Subhabrata, Park, Byeongju, Patel, Jaykumar, Pathak, Swetabh, Pattin, Alejandrina, Ankerst, Donna P, Peng, Jian, Petersen, Anne H, Philip, Robin, Piccolo, Stephen R, Pölsterl, Sebastian, Polewko-Klim, Aneta, Rao, Karthik, Ren, Xiang, Rocha, Miguel, Rudnicki, Witold R., Ryan, Charles J, Ryu, Hyunnam, Sartor, Oliver, Scherb, Hagen, Sehgal, Raghav, Seyednasrollah, Fatemeh, Shang, Jingbo, Shao, Bin, Shen, Liji, Sher, Howard, Shiga, Motoki, Sokolov, Artem, Söllner, Julia F, Song, Lei, Soule, Howard, Stolovitzky, Gustavo, Stuart, Josh, Sun, Ren, Sweeney, Christopher J, Tahmasebi, Nazanin, Tan, Kar-Tong, Tomaziu, Lisbeth, Usset, Joseph, Vang, Yeeleng S, Vega, Roberto, Vieira, Vitor, Wang, David, Wang, Difei, Wang, Junmei, Wang, Lichao, Wang, Sheng, Wang, Tao, Wang, Yue, Wolfinger, Russ, Wong, Chris, Wu, Zhenke, Xiao, Jinfeng, Xie, Xiaohui, Xie, Yang, Xin, Doris, Yang, Hojin, Yu, Nancy, Yu, Thomas, Yu, Xiang, Zahedi, Sulmaz, Zanin, Massimiliano, Zhang, Chihao, Zhang, Jingwen, Zhang, Shihua, Zhang, Yanchun, Zhou, Fang Liz, Zhu, Hongtu, Zhu, Shanfeng, Zhu, Yuxin, Winner, Kimberly Kanigel, Bare, J Christopher, Neto, Elias Chaibub, Peddinti, Gopal, and Scher, Howard I

Published
2017
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7. Identification of Broadly Applicable Adeno-Associated Virus Vectors by Systematic Comparison of Commonly Used Capsid Variants In Vitro

Author

Weinmann, Jonas, primary, Söllner, Julia, additional, Abele, Sarah, additional, Zimmermann, Gudrun, additional, Zuckschwerdt, Kai, additional, Mayer, Christine, additional, Danner-Liskus, Jenny, additional, Peltzer, Alexander, additional, Schuler, Michael, additional, Lamla, Thorsten, additional, and Strobel, Benjamin, additional

Published
2022
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8. Linking gene expression and orthology in mammals

Author

Söllner, Julia Franziska Elisabeth and Nieselt, Kay (apl. Prof. Dr.)

Subjects
Bioinformatik , Genexpression , Orthologie, gene expression, bioinformatics, orthology
Abstract

The overall aim of biomedical research is to understand disease mechanisms and to provide a drug to eventually cure the disease. This challenging endeavour requires an early research phase that deals with identifying target genes or proteins playing an important role in the disease. At this stage one uses animal models mimicking human disease to determine differences between healthy and diseased animals. Once potential drug targets have been found, compounds are screened and promising compounds go into the preclinical phase where their efficacy and, most importantly, safety are assessed. Those having proven to be efficacious and safe proceed to toxicology where the maximum tolerable dosage is assessed in, mainly, non-rodent species. According to the Bundesministerium für Ernährung und Landwirtschaft, more than 2 million animals were used for animal testing in German laboratories in 2017. The majority of these animals were mice and rats but also dogs, cats and monkeys are model organisms used for testing. While it is commonly accepted that other mammalian species resemble human biology to a great extent, one has to bear in mind that there are species-specific differences. One of the aims of this thesis was to investigate how similar widely used model species are to human and to each other on a molecular level. For this purpose we assessed the relationship between protein sequence identity and gene expression correlation with an emphasis on mouse and rat. We found that the majority of genes are highly similar, both on sequence and gene expression level. There were, however, cases with low sequence identity but high expression correlation. These cases were investigated in greater detail and the hypothesis that sequences annotated in widely used databases like Ensembl, UniProt, or RefSeq, may contain errors or are incomplete, was confirmed. Therefore, we investigated whether sequence information from related species can be used to derive a target’s sequence in a species with poor annotation. The a&o-tool was developed to exploit sequence similarity between related species and short-read RNA-Seq data to refine or validate target sequences. Since longread RNA-Seq data would greatly improve the results as entire transcripts are sequenced as a whole, we conducted a pilot study for comparing short- and long-read sequencing data. Even though PacBio’s SMRT sequencing technology still shows some issues with respect to data quality, it is a very promising approach that is going to prove valuable for sequence refinement. Another important goal of this thesis was to develop a score to assess a human target’s conservation across several model species. Publicly available data on the homology relationships between genes and RNA-Seq data build the basis for this score. Using a set of presumably highly conserved genes in human and mouse, we found that the proposed score yields reasonable results. An enrichment of Gene Ontology terms further strengthened our confidence in the conservation score.

Published
2020

11. Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data

Author

Guinney, Justin, primary, Wang, Tao, additional, Laajala, Teemu D, additional, Winner, Kimberly Kanigel, additional, Bare, J Christopher, additional, Neto, Elias Chaibub, additional, Khan, Suleiman A, additional, Peddinti, Gopal, additional, Airola, Antti, additional, Pahikkala, Tapio, additional, Mirtti, Tuomas, additional, Yu, Thomas, additional, Bot, Brian M, additional, Shen, Liji, additional, Abdallah, Kald, additional, Norman, Thea, additional, Friend, Stephen, additional, Stolovitzky, Gustavo, additional, Soule, Howard, additional, Sweeney, Christopher J, additional, Ryan, Charles J, additional, Scher, Howard I, additional, Sartor, Oliver, additional, Xie, Yang, additional, Aittokallio, Tero, additional, Zhou, Fang Liz, additional, Costello, James C, additional, Anghe, Catalina, additional, Azima, Helia, additional, Baertsch, Robert, additional, Ballester, Pedro J, additional, Bare, Chris, additional, Bhandari, Vinayak, additional, Dang, Cuong C, additional, Dunbar, Maria Bekker-Nielsen, additional, Buchardt, Ann-Sophie, additional, Buturovic, Ljubomir, additional, Cao, Da, additional, Chalise, Prabhakar, additional, Cho, Junwoo, additional, Chu, Tzu-Ming, additional, Coley, R Yates, additional, Conjeti, Sailesh, additional, Correia, Sara, additional, Dai, Ziwei, additional, Dai, Junqiang, additional, Dargatz, Philip, additional, Delavarkhan, Sam, additional, Deng, Detian, additional, Dhanik, Ankur, additional, Du, Yu, additional, Elangovan, Aparna, additional, Ellis, Shellie, additional, Elo, Laura L, additional, Espiritu, Shadrielle M, additional, Fan, Fan, additional, Farshi, Ashkan B, additional, Freitas, Ana, additional, Fridley, Brooke, additional, Fuchs, Christiane, additional, Gofer, Eyal, additional, Peddinti, Gopalacharyulu, additional, Graw, Stefan, additional, Greiner, Russ, additional, Guan, Yuanfang, additional, Guinney, Justin, additional, Guo, Jing, additional, Gupta, Pankaj, additional, Guyer, Anna I, additional, Han, Jiawei, additional, Hansen, Niels R, additional, Chang, Billy HW, additional, Hirvonen, Outi, additional, Huang, Barbara, additional, Huang, Chao, additional, Hwang, Jinseub, additional, Ibrahim, Joseph G, additional, Jayaswa, Vivek, additional, Jeon, Jouhyun, additional, Ji, Zhicheng, additional, Juvvadi, Deekshith, additional, Jyrkkiö, Sirkku, additional, Kanigel-Winner, Kimberly, additional, Katouzian, Amin, additional, Kazanov, Marat D, additional, Khayyer, Shahin, additional, Kim, Dalho, additional, Golinska, Agnieszka K, additional, Koestler, Devin, additional, Kokowicz, Fernanda, additional, Kondofersky, Ivan, additional, Krautenbacher, Norbert, additional, Krstajic, Damjan, additional, Kumar, Luke, additional, Kurz, Christoph, additional, Kyan, Matthew, additional, Laimighofer, Michael, additional, Lee, Eunjee, additional, Lesinski, Wojciech, additional, Li, Miaozhu, additional, Li, Ye, additional, Lian, Qiuyu, additional, Liang, Xiaotao, additional, Lim, Minseong, additional, Lin, Henry, additional, Lin, Xihui, additional, Lu, Jing, additional, Mahmoudian, Mehrad, additional, Manshaei, Roozbeh, additional, Meier, Richard, additional, Miljkovic, Dejan, additional, Mnich, Krzysztof, additional, Navab, Nassir, additional, Neto, Elias C, additional, Newton, Yulia, additional, Pal, Subhabrata, additional, Park, Byeongju, additional, Patel, Jaykumar, additional, Pathak, Swetabh, additional, Pattin, Alejandrina, additional, Ankerst, Donna P, additional, Peng, Jian, additional, Petersen, Anne H, additional, Philip, Robin, additional, Piccolo, Stephen R, additional, Pölsterl, Sebastian, additional, Polewko-Klim, Aneta, additional, Rao, Karthik, additional, Ren, Xiang, additional, Rocha, Miguel, additional, Rudnicki, Witold R., additional, Ryu, Hyunnam, additional, Scherb, Hagen, additional, Sehgal, Raghav, additional, Seyednasrollah, Fatemeh, additional, Shang, Jingbo, additional, Shao, Bin, additional, Sher, Howard, additional, Shiga, Motoki, additional, Sokolov, Artem, additional, Söllner, Julia F, additional, Song, Lei, additional, Stuart, Josh, additional, Sun, Ren, additional, Tahmasebi, Nazanin, additional, Tan, Kar-Tong, additional, Tomaziu, Lisbeth, additional, Usset, Joseph, additional, Vang, Yeeleng S, additional, Vega, Roberto, additional, Vieira, Vitor, additional, Wang, David, additional, Wang, Difei, additional, Wang, Junmei, additional, Wang, Lichao, additional, Wang, Sheng, additional, Wang, Yue, additional, Wolfinger, Russ, additional, Wong, Chris, additional, Wu, Zhenke, additional, Xiao, Jinfeng, additional, Xie, Xiaohui, additional, Xin, Doris, additional, Yang, Hojin, additional, Yu, Nancy, additional, Yu, Xiang, additional, Zahedi, Sulmaz, additional, Zanin, Massimiliano, additional, Zhang, Chihao, additional, Zhang, Jingwen, additional, Zhang, Shihua, additional, Zhang, Yanchun, additional, Zhu, Hongtu, additional, Zhu, Shanfeng, additional, and Zhu, Yuxin, additional

Published
2017
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14. Genetic code expansion, an emerging tool in the Ca 2+ ion channel field.

Author

Söllner J and Derler I

Subjects
Humans, Animals, Amino Acids genetics, Amino Acids metabolism, Calcium metabolism, Genetic Code, Calcium Channels genetics, Calcium Channels metabolism
Abstract

Various methods for characterizing binding forces as well as for monitoring and remote control of ion channels are still emerging. A recent innovation is the direct incorporation of unnatural amino acids (UAAs) with corresponding biophysical or biochemical properties, which are integrated using genetic code expansion technology. Minimal changes to natural amino acids, which are achieved by chemical synthesis of corresponding UAAs, are valuable tools to provide insight into the contributions of physicochemical properties of side chains in binding events. To gain unique control over the conformational changes or function of ion channels, a series of light-sensitive, chemically reactive and posttranslationally modified UAAs have been developed and utilized. Here, we present the existing UAA tools, their mode of action, their potential and limitations as well as their previous applications to Ca 2+ -permeable ion channels., (© 2024 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Published
2024
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15. Insights into the dynamics of the Ca2+ release-activated Ca2+ channel pore-forming complex Orai1.

Author

Fröhlich M, Söllner J, and Derler I

Subjects
Animals, Humans, Calcium Signaling, Cell Membrane metabolism, Calcium metabolism, Calcium Release Activated Calcium Channels metabolism, Endoplasmic Reticulum metabolism, ORAI1 Protein metabolism, Stromal Interaction Molecule 1 metabolism
Abstract

An important calcium (Ca2+) entry pathway into the cell is the Ca2+ release-activated Ca2+ (CRAC) channel, which controls a series of downstream signaling events such as gene transcription, secretion and proliferation. It is composed of a Ca2+ sensor in the endoplasmic reticulum (ER), the stromal interaction molecule (STIM), and the Ca2+ ion channel Orai in the plasma membrane (PM). Their activation is initiated by receptor-ligand binding at the PM, which triggers a signaling cascade within the cell that ultimately causes store depletion. The decrease in ER-luminal Ca2+ is sensed by STIM1, which undergoes structural rearrangements that lead to coupling with Orai1 and its activation. In this review, we highlight the current understanding of the Orai1 pore opening mechanism. In this context, we also point out the questions that remain unanswered and how these can be addressed by the currently emerging genetic code expansion (GCE) technology. GCE enables the incorporation of non-canonical amino acids with novel properties, such as light-sensitivity, and has the potential to provide novel insights into the structure/function relationship of CRAC channels at a single amino acid level in the living cell., (© 2024 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Published
2024
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