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Federica Briani
2016
BIOGRAPHICAL SKETCH
NAME
Federica Briani
ORCID ID: orcid.org/0000-0002-5876-4463
[email protected]
POSITION TITLE
Assistant professor (Ricercatore confermato)
Dipartimento di Bioscienze
Università degli Studi di Milano
EDUCATION/TRAINING
INSTITUTION AND LOCATION
Universita' degli Studi di Milano (UNIMI)
Universita' degli Studi di Milano (UNIMI)
DEGREE
Master
Degree
(Laurea a ciclo
unico)
PhD in
Genetics
YEAR
1992
1996
FIELD OF STUDY
Biology
Bacteriophage molecular
genetics
Positions and Honors
Positions and Employment
1996-1997 Post-doctoral Fellow, Telethon Institute of Genetics and Medicine, Milan
1997-2002 Post-doctoral Fellow, UNIMI
2002Assistant professor at UNIMI
Other Experience and Professional Memberships
1999
CNR short-term fellow for short-term stay at the Institut de Biologie Physico-Chimique, Paris
2001Member, Italian Genetics Society (AGI)
2007Member, Italian Microbiology and Biotechnology Society (SIMGBM)
2016Executive committee member of SIMGBM
Honors
1996
2014
SIMGBM award for the best Italian Ph.D. thesis in the field of Microbial Genetics.
Winner of the Discovery Fast Track Challenge 2014 of GlaxoSmithKline
Scientific activity
REGULATION OF THE LYSOGENIC STATE OF BACTERIOPHAGE P4
As a PhD student and postdoctoral fellow in the laboratory of prof. G. Dehò, I studied the lysogenic state regulation of
the E. coli bacteriophage P4. The mechanism of immunity to superinfection of prophage P4 has some aspects that make
it very peculiar. In fact, P4 immunity is not exercised through repression of transcription initiation of lytic genes, but
causing premature termination of transcription of the operon containing these genes. In addition, the factor of
immunity is not a protein, but a small RNA with regulatory function (CI RNA), which is produced by maturation of the
primary transcript by RNase P and polynucleotide phosphorylase (PNPase).
Federica Briani
2016
My work led to the identification of three terminators whose activity is regulated by CI RNA and by elements of the
untranslated leader region of the lytic operon. I also studied the maturation of P4 CI RNA , identifying both structural
elements required in cis for the production of CI and factors of the E. coli host (RNase E and polyadenylpolymerase I),
which, together with PNPase, are involved in this process.
1. Briani, F., Zangrossi, S., Ghisotti, D., and Dehò, G. (1996) A Rho-dependent transcription termination site regulated
by bacteriophage P4 RNA immunity factor. Virology 223: 57-67.
2.Piazza, F., Zappone, M., Sana, M., Briani, F., and Dehò, G. (1996) Polynucleotide phosphorylase of Escherichia coli is
required for the establishment of bacteriophage P4 immunity. J. Bacteriol. 178: 5513-5521
3. Briani, F., Ghisotti, D., and Dehò, G. (2000) Antisense RNA-dependent transcription termination sites that modulate
lysogenic development of satellite phage P4. Mol. Microbiol. 36:1124-1134.
4. Briani, F., Del Vecchio, E., Migliorini, D., Hajnsdorf, E., Régnier, P., Ghisotti, D., and Dehò, G. (2002) RNase E and
polyadenylpolymerase I are involved in maturation of CI RNA, the P4 phage immunity factor. J. Mol. Biol. 318:
321-331.
ESCHERICHIA COLI PNPASE
The study of CI RNA processing led me to study the more general role that one of the factors involved in this process,
PNPase, plays in the post-transcriptional regulation of gene expression in E. coli. PNPase, which is essential in E. coli for
growth in the cold, catalyzes the phosphorolytic degradation of RNA in the 3'-5 ‘ direction. The enzyme consists of three
identical subunits encoded by pnp gene and interacts with other proteins (RNase E, RhlB and enolase) forming a high
molecular weight complex, the RNA degradosome. The physiological role of this interesting protein was analyzed from
different points of view and my main contribution to this research were as follows.
1. New insights in structure-function relationships of PNPase
I coordinated a project aimed at the systematic mutagenesis of the pnp gene and the functional characterization of the
point mutants obtained. The results of this research have shown that both the RNA binding and the phosphorolytic
activity of the enzyme are necessary for growth in the cold and have implicated in the catalytic activity of PNPase the "all
alpha-helical" domain, whose function was unknown. A point mutant, pnp-G454D, was analyzed more finely and I
showed that other regions of PNPase, besides the two "RNA-binding" S1 and KH domains, localized at the C-terminus,
contribute to the binding to the RNA.
2. PNPase autoregulation
PNPase posttranscriptionally regulates its own expression. We provide evidence supporting a new pathway for PNPase
autogenous regulation in which PNPase acts as a translational repressor of its own primary transcript. Our data make a
new contribution to the understanding of the regulatory mechanism of pnp mRNA, a process long since considered a
paradigmatic example of posttranscriptional regulation at the level of mRNA stability.
3. PNPase and biofilm formation
We observed that biofilm formation is greatly stimulated in mutants lacking PNPase. The study of this phenomenon,
which I coordinated in collaboration with prof. P. Landini (UNIMI), has shown that PNPase negatively regulates the
production of poly-N-acetyl glucosamine (PNAG), an exopolysaccharide which is an important adhesion factor in E. coli
and other bacteria.
1. Regonesi, M.E., & Briani, F., Ghetta, A., Zangrossi, S., Ghisotti, D., Tortora, P., and Dehò, G. (2004) A mutation in
polynucleotide phosphorylase from Escherichia coli impairing RNA binding and degradosome stability. Nucl. Acids
Res. 32: 1006-1017.
2. Briani, F., Del Favero, M., Capizzuto, R., Consonni, C., Zangrossi, S., Greco, C., De Gioia, L., Tortora, P., and Dehò, G.
(2007) Genetic Analysis of Polynucleotide Phosphorylase Structure and Functions. Biochimie 89:145-157
3. T. Carzaniga, D. Antoniani, G. Dehò, F. Briani & P. Landini.(2012) The RNA processing enzyme polynucleotide
phosphorylase negatively controls biofilm formation by repressing poly-N-acetylglucosamine (PNAG) production in
Escherichia coli C. BMC Microbiology. 12, article 270
4. T. Carzaniga, G. Dehò, F. Briani (2015) RNase III-independent autogenous regulation of Escherichia coli
polynucleotide phosphorylase via translational repression. J. Bact. 197(11):1931-8
RIBOSOMAL PROTEIN S1
The regulation of mRNA stability and translatability is an important step in the post-transcriptional control of gene
expression. A line of research that I coordinated has shown that in vivo overexpression of the ribosomal protein S1 (an
atypical ribosomal protein that is weakly associated with the 30S subunit of the ribosome) causes the inhibition of
Federica Briani
2016
translation and a remarkable stabilization of pnp mRNA. In successive studies I have shown that this phenomenon is not
restricted to pnp mRNA, as different full length mRNA are also stabilized through specific inhibition of RNase Edependent degradation. This phenomenon may represent a regulative strategy to modulate gene expression in response
to physiological fluctuations of mRNA translation efficiency. I translated my theoretical studies on S1 protein to the
development of an assay aimed at the identification of new antibiotics inhibiting translation initiation. This allowed me
to be one of the winners of the 2014 Discovery Fast Track competition of GlaxoSmithKline.
1. Briani, F., Curti, S., Rossi, F., Carzaniga, T., Mauri P., and Dehò, G. (2008) Polynucleotide phosphorylase hinders
mRNA degradation upon translational stress induced by ribosomal protein S1 in Escherichia coli. RNA 14:2417-29
2. Delvillani, F., Papiani, G., Dehò, G., and Briani, F. (2011). S1 ribosomal protein and the interplay between
translation and mRNA decay. Nucl. Acids Res. 39(17):7702-15
3. Raneri, M., Sciandrone, B., Briani, F. (2015) A Whole-Cell Assay for Specific Inhibitors of Translation Initiation in
Bacteria. J. Biomol.Screening. 20(5):627-33
4. http://openinnovation.gsk.com/na/winners.php
ANALYSIS OF RNA-BASED REGULATION IN PSEUDOMONAS AERUGINOSA
Two classes of riboregulators have been the object of my research on P. aeruginosa:
1. Small non coding RNAs. In collaboration with the group of. G. Bertoni (UNIMI), we have identified around 150 new
sRNAs of P. aeruginosa by SRNA-Seq and validated the expression of 55 of these by Northern blotting, substantially
increasing the number of sRNAs of P. aeruginosa identified so far.
2. RNA thermometers. I developed a genetic system, the Tet-Trap, which allowed the identification of four new putative
RNA thermometers. Two of them have been validated. Interestingly, they regulate the expression of virulence-relevant
genes of P. aeruginosa that regulate glucose utilization and lipopolysaccharide modification (i.e. ptxS and lpxT,
respectively). My current research activity stems from these results and concerns the regulation of the orthologous E.
coli lpxT gene and the physiological role of ptxS and response to glucose in P. aeruginosa.
1. Ferrara, S., Brugnoli, M., De Bonis, A., Righetti, F., Delvillani, F., Dehò, G., Horner, D., Briani, F., & Bertoni, G. (2012)
Comparative Profiling of Pseudomonas aeruginosa Strains Reveals Differential Expression of Novel Unique and
Conserved Small RNAs. PlosOne 7(5):e36553
2. Delvillani, F., Sciandrone, B., Peano, C., Petiti, L., Berens, C., Georgi, C., Ferrara, S., Bertoni, G., Pasini, ME, Dehò, G.,
Briani, F. (2014) Tet-Trap, a genetic approach to the identification of bacterial RNA thermometers: application to
Pseudomonas aeruginosa. RNA. 20: 1963-1976
A complete list of my publications is attached as a separate file and can also be found at http://orcid.org/0000-00025876-4463.
Teaching activity
Current activity
General Microbiology (Microbiologia generale; 9 CFUs), Bachelor Degree in Scienze biologiche, Università degli Studi di
MIlano (since 2015)
Cellular and Molecular Microbiology (the course is in English; 6 CFUs), Master Degree in Molecular Biotechnology and
Bioinformatics, Università degli Studi di MIlano (since 2008)
Bacterial genetics (Genetica dei Microrganismi; 1CFU), Post-Graduation School in Microbiology and Virology (Scuola di
specializzazione in Microbiologia e Virologia) Università degli Studi di MIlano (since 2009)
Past activity
Introduzione alla Biologia della Cellula, Bachelor Degree in Scienze Biologiche (2 CFUs)
Genetica dei Microrganismi, Degree in Scienze Biologiche (ciclo unico), Università degli Studi dell’Insubria di Varese
Practicals in Genetics, Degree in Scienze biologiche (1997-2004)