Article
Biochemistry & Molecular Biology
Aditya Mojumdar, Nancy Adam, Jennifer A. Cobb
Summary: The two major pathways of DNA double-strand break repair, nonhomologous end-joining and homologous recombination, are highly conserved from yeast to mammals. Nej1 interacts with Sae2 to impact DSB repair in three ways: inhibiting the interaction of Sae2 with the Mre11-Rad50-Xrs2 complex and its localization to DSBs, inhibiting Sae2-dependent recruitment of Dna2 independently of Sgs1, and showing an epistatic relationship with SAE2 for end-bridging. These findings provide mechanistic insight on how Nej1 functionality inhibits the initiation of DNA resection, a role distinct from its involvement in endjoining repair at DSBs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Microbiology
Areum Lee, Eunji Bae, Jihee Park, Kyoung-Hwa Choi, Jaeho Cha
Summary: The study identified the genes responsible for glycogen synthesis (glgA and amyA) and degradation (glgX and gaa) in Sulfolobus acidocaldarius. It showed that the glycogen deficient strain had a higher death rate in nutrient limited conditions, suggesting that glycogen in S. acidocaldarius supports cell maintenance in harsh conditions.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Kerstin Rastaedter, David J. Wurm, Oliver Spadiut, Julian Quehenberger
Summary: This study analyzed and compared the influence of two different types of spargers on Pg/Vl and kla in a 2 L chemostat cultivation of S. acidocaldarius at 75 degrees C and a pH value of 3.0. The scale-up criterion kLa was then used to scale up to 20 L and 200 L. By maintaining a constant kla value, comparable dry cell weight, specific growth rate, specific substrate uptake rates, and viability were observed between all investigated scales. This procedure holds the potential for further scaling up to industrial-sized bioreactors.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Jens C. Benninghoff, Laura Kuschmierz, Xiaoxiao Zhou, Andreas Albersmeier, Trong Khoa Pham, Tobias Busche, Phillip C. Wright, Jorn Kalinowski, Kira S. Makarova, Christopher Brasen, Hans-Curt Flemming, Jost Wingender, Bettina Siebers
Summary: Sulfolobus acidocaldarius, a thermoacidophilic crenarchaeon, shows high tolerance to the industrial organic solvent 1-butanol. Exposure to 1-butanol enhances biofilm formation, changes cell morphology, and alters cellular responses at the transcriptional and proteomic levels. This extremophile's extreme lifestyle coincides with a global cellular response to organic solvents, providing insights into biofilm formation and membrane/cell stress in S. acidocaldarius.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Aleksei Samolygo, Januka S. Athukoralage, Shirley Graham, Malcolm F. White
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Kawanda Foster, Sabine Gruschow, Scott Bailey, Malcolm F. White, Michael P. Terns
NUCLEIC ACIDS RESEARCH
(2020)
Article
Biochemical Research Methods
Reyes Sanles-Falagan, Biljana Petrovic-Stojanovska, Malcolm F. White
PROTEIN EXPRESSION AND PURIFICATION
(2020)
Article
Biology
Januka S. Athukoralage, Shirley Graham, Christophe Rouillon, Sabine Gruschow, Clarissa M. Czekster, Malcolm F. White
Article
Biochemistry & Molecular Biology
Wenlong Zhu, Stuart McQuarrie, Sabine Gruschow, Stephen A. McMahon, Shirley Graham, Tracey M. Gloster, Malcolm F. White
Summary: A newly discovered CARF family effector named Can2 is found to provide effective immunity against plasmid transformation and bacteriophage infection in Escherichia coli by being activated by cyclic tetra-adenylate (cA(4)) and displaying both DNase and RNase activity. The structure of Can2 in complex with cA(4) reveals a potential mechanism for the cA(4)-mediated activation of the enzyme, where an active site cleft is exposed upon activator binding. These findings enhance our understanding of type III CRISPR cOA signaling and effector function.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Januka S. Athukoralage, Malcolm F. White
Summary: In prokaryotes, CRISPR-Cas immune systems defend against mobile genetic elements by recognizing and cleaving foreign nucleic acids. Type III CRISPR-Cas complexes also synthesize cyclic oligoadenylate (cOA) second messengers, which activate antiviral defense proteins but require mechanisms to eliminate cOA to aid in cell recovery. The degradation of cOA by ring nucleases specifically switches off CRISPR ancillary enzymes and regulates the cOA signaling pathway.
Article
Biochemistry & Molecular Biology
Sabine Gruschow, Catherine S. Adamson, Malcolm F. White
Summary: Type III CRISPR systems detect and defend against RNA invaders through the activation of Cas10. The effector nucleases are activated via cyclic oligoadenylate (cOA) second messenger molecules. The specificity and sensitivity of the VmeCmr system make it a potentially valuable tool for detecting SARS-CoV-2 virus RNA.
NUCLEIC ACIDS RESEARCH
(2021)
Editorial Material
Multidisciplinary Sciences
Catrin Pritchard, Malcolm F. White, Steve Brown
ROYAL SOCIETY OPEN SCIENCE
(2022)
Article
Virology
Januka S. Athukoralage, Malcolm F. White
Summary: Recent advances in our understanding of prokaryotic antiphage defense mechanisms have revealed multiple new cyclic nucleotide signaling molecules that play crucial roles in switching infected cells into an antiviral state.
ANNUAL REVIEW OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Gaelle Hogrel, Abbie Guild, Shirley Graham, Hannah Rickman, Sabine Gruschow, Quentin Bertrand, Laura Spagnolo, Malcolm F. White
Summary: Cyclic nucleotide signalling plays a key role in antiviral defence. Viral detection activates nucleotide cyclase, leading to the activation of effector proteins. This study reveals a bacterial antiviral defence system that assembles an extended superhelical solenoid structure through the binding of cyclic tri-adenylate and TIR-SAVED effector, and provides important insights into the mechanism of TIR enzyme activation.
Article
Biochemistry & Molecular Biology
Qilin Shangguan, Shirley Graham, Ramasubramanian Sundaramoorthy, Malcolm F. White
Summary: The composition, structure, and function of the type I-G Cascade CRISPR effector from Thioalkalivibrio sulfidiphilus have been studied, revealing key new molecular details. These findings shed light on the diversity of type I systems and open new avenues for genome engineering applications.
NUCLEIC ACIDS RESEARCH
(2022)
Correction
Multidisciplinary Sciences
Galle Hogrel, Abbie Guild, Shirley Graham, Hannah Rickman, Sabine Gruschow, Quentin Bertrand, Laura Spagnolo, Malcolm F. White
Article
Multidisciplinary Sciences
Christophe Rouillon, Niels Schneberger, Haotian Chi, Katja Blumenstock, Stefano Da Vela, Katrin Ackermann, Jonas Moecking, Martin F. Peter, Wolfgang Boenigk, Reinhard Seifert, Bela E. Bode, Jonathan L. Schmid-Burgk, Dmitri Svergun, Matthias Geyer, Malcolm F. White, Gregor Hagelueken
Summary: CRISPR defence systems are widespread in prokaryotes, and the type III systems initiate a complex antiviral response through the synthesis of cyclic oligoadenylates after recognition of foreign RNA. The CRISPR-associated Lon protease (CalpL) is linked to type III systems and binds cyclic oligoadenylates. This study reveals that CalpL forms a stable complex with two other proteins, CalpT and CalpS, and specifically cleaves CalpT to release CalpS, connecting CRISPR-based detection of foreign nucleic acids and transcriptional regulation.
Article
Biochemistry & Molecular Biology
Stuart McQuarrie, Januka S. Athukoralage, Stephen A. McMahon, Shirley Graham, Katrin Ackermann, Bela E. Bode, Malcolm F. White, Tracey M. Gloster
Summary: Type III CRISPR systems produce cOA second messengers to activate defense nucleases against invading mobile genetic elements. Csm6 ribonucleases bind cOA and undergo conformational changes that trigger mRNA destruction. Understanding this activation mechanism is important for developing diagnostic assays.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Giuseppe Cannone, Dmytro Kompaniiets, Shirley Graham, Malcolm F. White, Laura Spagnolo
Summary: CRISPR-Cas is an adaptive immune system found in prokaryotes, classified into six types based on signature proteins. Type III systems, classified by the presence of a Cas10 subunit, are diverse multisubunit assemblies with various enzymatic activities and downstream effectors. Though most biotechnological CRISPR applications use proteins from Type II, recent developments have shown the feasibility and effectiveness of multi-protein Type III CRISPR-Cas effector complexes as RNA-targeting tools in eukaryotes. This study reports the cryo-EM structure of the Type III-D complex (SsoCsm) from Saccharolobus solfataricus, providing insights into its organization, subunit connectivity, and protein-RNA interactions.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2023)