Special School Seminar - The genuine CRISPR and applications thereof

Dr Francisco Mojica, Senior Lecturer, Department of Physiology, Genetic and Microbiology, University of Alicante, Spain.

Arrays of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) were discovered three decades ago. Soon after, during the early 1990s, the first functional analyses were carried in extremely halophilic archaea, where these repeats were shown to interfere with DNA replicon maintenance when manipulated. Afterwards, CRISPR were reported in additional, distantly related prokaryotes, leading to the recognition of a new family of short regularly spaced repeats, widespread in bacteria and archaea. The identification of CRISPR-associated (Cas) proteins and the revelation that repeat-intervening sequences (referred to as spacers) seemed to be incompatible with matching sequences in mobile genetic elements (notably, in viruses, suggesting a defensive function), fueled research on CRISPR-Cas. As a result, their role as an adaptive immune system was soon demonstrated for a variety of model microorganisms, and the mechanism of action unveiled. Subsequently, a three-step (i.e., adaptation, expression and interference) general scheme was conceived, involving the common elements of active CRISPR-Cas systems: repeats, spacers, Cas proteins and the “leader” sequences (AT-rich stretches flanking CRISPR arrays). In brief, during adaptation, new spacers are integrated at the leader-proximal end of a CRISPR cassette. Transcription from the leader, and processing of the CRISPR transcript (expression stage), generates single-spacer CRISPR RNA (crRNA) molecules that guide a Cas endonuclease to targeted sequences (complementary to the carried spacer), leading to target cleavage (interference). The unique combination of versatility and feasibility of the diverse CRISPR-Cas components enables a variety of applications, not only in the native carrier organism but also in heterologous (prokaryotic or eukaryotic) hosts. Hitherto, native and engineered interference-related elements of CRISPR-Cas have been harnessed for host immunization, cell dormancy, regulation of gene expression, locus labelling, molecular diagnostics and genome editing, in almost any cell type, from prokaryotes and plant cells to neurons. More recently, the adaptation capability of CRISPR has also been exploited, utilizing the repeat-spacer arrays as data storage devices in bacteria. Thanks to the prokaryotes, we have on our hands the most powerful tools ever available for biological and biomedical research, revolutionizing biotechnology, agriculture and medicine. Still, the use of CRISPR-Cas as therapeutic agents in humans, looks very promising to tackle major challenges in clinical practice.

Francisco Juan Martínez Mojica (born 5 October 1963, Elche, Spain), is Associate Professor of Microbiology at the Department of Physiology, Genetics and Microbiology, University of Alicante (Spain). He graduated in Biology from the University of Valencia (Spain, 1986). In 1993, he earned his PhD. in Biology, for research on the response of halophilic microorganisms to stress factors (University of Alicante), under supervision by Dr. Francisco E. Rodríguez Valera and Dr. Guadalupe Juez Pérez. During the stage of elaboration of his thesis, he visited the laboratory of Dr. Patrick Forterre at the University Paris XI (Orsay, France, 1991-1992) where he began in the analysis of the DNA structure. He carried out postdoctoral research work on bacterial motility at the University of Utah (USA; 1993) with Dr. John S. Parkinson (University of Utah, Salt Lake City, USA, 1993) and on gene regulation and DNA topology at the lab led by Dr. Christopher F. Higgins at the University of Oxford
(UK; 1995-1996). In 1997, he returned to the University of Alicante to hold a faculty position as professor of Microbiology, founding the Molecular Microbiology group.

Dr Mojica's visit to Australia is co-funded by the Spanish Researchers in Australia - Pacific (SRAP).

Date & time

10–11am 14 June 2018

Location

The Finkel Lecture Theatre, The John Curtin School of Medical Research, Building 131, Garran Road, ANU

Speakers

Dr Francisco Mojica

Contacts

 Dr Anne-Sophie Dielen
 +61 2 6125 2577

Updated:  15 August 2018/Responsible Officer:  Director, JCSMR/Page Contact:  Web Manager