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Università della Svizzera italiana

Crossover or non-crossover outcomes : tailored processing of homologous recombination intermediates

Sanchez, Aurore ; Reginato, Giordano ; Cejka, Petr

In: Current opinion in genetics & development, 2021, vol. 71, p. 39-47

DNA breaks may arise accidentally in vegetative cells or in a programmed manner in meiosis. The usage of a DNA template makes homologous recombination potentially error-free, however, recombination is not always accurate. Cells possess a remarkable capacity to tailor processing of recombination intermediates to fulfill a particular need. Vegetatively growing cells aim to maintain genome...

Università della Svizzera italiana

Structure and function analysis of an antibody recognizing all influenza A subtypes

Kallewaard, Nicole L. ; Corti, Davide ; Collins, Patrick J. ; Neu, Ursula ; McAuliffe, Josephine M. ; Benjamin, Ebony ; Wachter-Rosati, Leslie ; Palmer-Hill, Frances J. ; Yuan, Andy Q. ; Walker, Philip A. ; Vorlaender, Matthias K. ; Bianchi, Siro ; Guarino, Barbara ; De Marco, Anna ; Vanzetta, Fabrizia ; Agatic, Gloria ; Foglierini, Mathilde ; Pinna, Debora ; Fernandez-Rodriguez, Blanca ; Fruehwirth, Alexander ; Silacci, Chiara ; Ogrodowicz, Roksana W. ; Martin, Stephen R. ; Sallusto, Federica ; Suzich, JoAnn A. ; Lanzavecchia, Antonio ; Zhu, Qing ; Gamblin, Steven J. ; Skehel, John J.

In: Cell, 2016, vol. 166, no. 3, p. 596-608

Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when...

Università della Svizzera italiana

The antibody response to Plasmodium falciparum : cues for vaccine design and the discovery of receptor-based antibodies

Tan, Joshua ; Piccoli, Luca ; Lanzavecchia, Antonio

In: Annual Review of Immunology

P. falciparum remains a serious public health problem and a continuous challenge for the immune system due to the complexity and diversity of the pathogen. Recent advances from several laboratories in the characterization of the antibody response to the parasite have led to the identification of critical targets for protection and revealed a new mechanism of diversification based on the...

Università della Svizzera italiana

Identification and structure of a multidonor class of head-directed influenza-neutralizing antibodies reveal the mechanism for its recurrent elicitation

Sao-Fong Cheung, Crystal ; Fruehwirth, Alexander ; Paparoditis, Philipp Carl Georg ; Shen, Chen-Hsiang ; Foglierini, Mathilde ; Joyce, M. Gordon ; Leung, Kwanyee ; Piccoli, Luca ; Rawi, Reda ; Silacci-Fregni, Chiara ; Tsybovsky, Yaroslav ; Verardi, Raffaello ; Wang, Lingshu ; Wang, Shuishu ; Yang, Eun Sung ; Zhang, Baoshan ; Zhang, Yi ; Chuang, Gwo-Yu ; Corti, Davide ; Mascola, John R. ; Shapiro, Lawrence ; Kwong, Peter D. ; Lanzavecchia, Antonio ; Zhou, Tongqing

In: Cell reports, 2020, vol. 32, no. 9, p. 12 p

Multidonor antibodies are of interest for vaccine design because they can in principle be elicited in the general population by a common set of immunogens. For influenza, multidonor antibodies have been observed against the hemagglutinin (HA) stem, but not the immunodominant HA head. Here, we identify and characterize a multidonor antibody class (LPAF-a class) targeting the HA head. This class...

Università della Svizzera italiana

Antibody-guided vaccine design : identification of protective epitopes

Lanzavecchia, Antonio ; Frühwirth, Alexander ; Perez, Laurent ; Corti, Davide

In: Current opinion in immunology, 2016, vol. 41, no. August, p. 62-67

In the last decade, progress in the analysis of the human immune response and in the isolation of human monoclonal antibodies have provided an innovative approach to the identification of protective antigens which are the basis for the design of vaccines capable of eliciting effective B-cell immunity. In this review we illustrate, with relevant examples, the power of this approach that can...

Università della Svizzera italiana

A LAIR-1 insertion creates broadly reactive antibodies against malaria variant antigens

Tan, Joshua ; Pieper, Kathrin ; Piccoli, Luca ; Abdi, Abdirahman ; Tully, Claire Maria ; Foglierini Perez, Mathilde ; Geiger, Roger ; Jarrossay, David ; Maina Ndungu, Francis ; Wambua, Juliana ; Bejon, Philip ; Silacci Fregni, Chiara : Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland ; Fernandez-Rodriguez, Blanca ; Barbieri, Sonia ; Bianchi, Siro ; Marsh, Kevin ; Thathy, Vandana ; Corti, Davide ; Sallusto, Federica ; Bull, Peter ; Lanzavecchia, Antonio

In: Nature, 2016, vol. 529, p. 25 p

Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies1,2,3,4. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their...

Université de Fribourg

Auxin-transporting ABC transporters are defined by a conserved D/E-P motif regulated by a prolylisomerase

Hao, Pengchao ; Xia, Jian ; Liu, Jie ; Donato, Martin Di ; Pakula, Konrad ; Bailly, Aurélien ; Jasinski, Michal ; Geisler, Markus

In: Journal of Biological Chemistry, 2020, vol. 295, no. 37, p. 13094–13105

The plant hormone auxin must be transported throughout plants in a cell-to-cell manner to affect its various physiological functions. ABCB transporters are critical for this polar auxin distribution, but the regulatory mechanisms controlling their function is not fully understood. The auxin transport activity of ABCB1 was suggested to be regulated by a physical interaction with FKBP42/Twisted...

Università della Svizzera italiana

Thioredoxin-related transmembrane proteins : TMX1 and little brothers TMX2, TMX3, TMX4 and TMX5

Guerra, Concetta ; Molinari, Maurizio

In: Cells, 2020, vol. 9, no. 9, p. 11 p

The endoplasmic reticulum (ER) is site of synthesis and maturation of membrane and secretory proteins in eukaryotic cells. The ER contains more than 20 members of the Protein Disulfide Isomerase (PDI) family. These enzymes regulate formation, isomerization and disassembly of covalent bonds between cysteine residues. As such, PDIs ensure protein folding, which is required to attain functional...

Université de Fribourg

Mitochondrial sphingosine-1-phosphate lyase is essential for phosphatidylethanolamine synthesis and survival of Trypanosoma brucei

Dawoody Nejad, Ladan ; Stumpe, Michael ; Rauch, Monika ; Hemphill, Andrew ; Schneiter, Roger ; Bütikofer, Peter ; Serricchio, Mauro

In: Scientific Reports, 2020, vol. 10, no. 1, p. 8268

Sphingosine-1-phosphate is a signaling molecule involved in the control of cell migration, differentiation, survival and other physiological processes. This sphingolipid metabolite can be degraded by the action of sphingosine-1-phosphate lyase (SPL) to form hexadecenal and ethanolamine phosphate. The importance of SPL-mediated ethanolamine phosphate formation has been characterized in only...

Università della Svizzera italiana

The MRE11 complex : a versatile toolkit for the repair of broken DNA

Reginato, Giordano ; Cejka, Petr

In: DNA repair, 2020, vol. 91–92, no. July–August, p. 13 p

When DNA breaks, the ends need to be stabilized and processed to facilitate subsequent repair, which can occur by either direct but error-prone end-joining with another broken DNA molecule or a more accurate homology-directed repair by the recombination machinery. At the same time, the presence of broken DNA triggers a signaling cascade that regulates the repair events and cellular progression...