A PhD position is available, starting on Nov 1, 2016, on the project "OPTOGENETIC MODULATION OF GENE TRANSCRIPTION". Deadline for the application is June 8th, 2016. For more info please contact me at email@example.com
I obtained a Master's degree summa cum laude in Biological Sciences at the University of Padua. After my degree I moved to London, where I attained a PhD in biochemistry at the University College of London, working in the laboratory of Dr. Schiavo at Cancer Research UK. I then moved to IIT, in Genova, where I currently hold a Researcher position in the group led by Dr. Benfenati.
I have spent most of my career working in the neuroscience field. During my PhD and postdoc, I have worked on axonal transport, intracellular trafficking and signaling, mouse genetics and development, physiology of neurotrophins, and synaptic vesicle recycling. I have recently approached the new and exciting field of optogenetics, and I am now supervising a number of projects dealing with the development and validation of new optogenetic probes for in vitro and in vivo applications. In addition, I am involved in a number of collaborative projects, all EU-funded, aimed at characterizing new biocompatible materials for nervous system regeneration.
Molecular Mechanisms of Growth Factor Receptor Cross-Talk and Neuronal Excitability.
This project aims at understanding how different trophic pathways interplay and cross-talk with each other during nervous system development. A protein likely to play a role in this process is Kinase D interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS). Kidins220 is a conserved membrane protein preferentially expressed in the nervous system. Kidins220 interacts with neurotrophin, ephrin, vascular endothelial growth factor (VEGF) and glutamate receptors, and is a common downstream target of several trophic stimuli. In some recent publications, we describe the generation and characterization of a number of Kidins220 full and conditional knockout mouse lines, which are presently available in the Institute. Kidins220-/-embryos die at late stages of gestation, and show extensive cell death in the central and peripheral nervous systems. The neuronal-specific deletion of this protein leads to early postnatal death, showing that Kidins220 also has a critical function in the postnatal brain.
The project is currently focusing on the following topics:
(i) Effects of Kidins220 ablation in postnatal cortical development, in terms of proliferation of precursor cells, neurodegeneration and neuronal migration. For these studies, we are using the CaMKII-Kidins220 conditional line, specifically driving Kidins220 ablation in postnatal forebrain excitatory neurons.
(ii) Role of Kidins220 in synaptic physiology and neuronal excitability. Transmission and coding of information in neural networks relies on the maintenance of a proper balance between the levels of excitation and inhibition. We have recently shown that Kidins220 plays a role in the mechanisms regulating the recovery of synaptic strength in GABAergic synapses. In addition, our preliminary data show that Kidins220 interacts with Nav channels. Being responsible to determine the onset of action potentials at the axonal initial segment, voltage-gated Nav channels are fundamental players in all kinds of neuronal communication. Factors that can modulate Nav functionality are therefore of great interest in the field of neurophysiology. We are presently characterizing the biological significance of the Kidins220-Nav interaction, focusing on the mechanisms by which Kidins220 can regulate Nav localization and activity.
Design and Characterization of Novel Optogenetic Probes.
This project involves the designing, engineering and validating of a series of novel optogenetic probes and sensors.
(i) Light-sensitive probes to modulate gene transcription. Such probes are obtained by fusing light-sensitive (Light-Oxygen-Voltage, LOV) domains to specific modulators of transcription. In particular, we plan to target the activity of the transcriptional repressor REST/NRSF (RE1-silencing transcription factor / neuron-restrictive silencer factor). REST acts mainly by repressing neural-specific genes in non-neuronal tissues, however, recent evidence show that REST is present also in the nervous system. REST expression increases under pathological conditions such as ischemia and epileptic seizures, where it can have either protective or neurodegenerative effects. Our light-sensitive probes will allow us to reversibly modulate REST action, thus re-establishing the physiological pattern of transcription, both in vitro and in vivo.
(ii) Fluorescence-based indicators of extracellular pH. Acidic shifts of extracellular pH are often the consequence of pathological insults such as epileptic seizures, and are associated to neuronal depolarization and hyper-excitability. We are presently validating a series of probes based on pH-sensitive variants of fluorescent proteins, which will allow us to visualize in real time pH oscillations in healthy and diseased brains. These pH-sensitive probes will be subsequently fused to inhibitory opsins, such as Arch or Acetabularia rodhopsin. In this “combinatorial” construct GFP fluorescence will increase at low (pathological) pH, thus activating the opsin. The activated opsin would in turn hyper-polarize the neuron, dampening the depolarization caused by the low pH environment, thus keeping the excitability of the neural network into the physiological range.
Biocompatible materials for nervous system regeneration.
We are working on engineering biocompatible interfaces able to support and drive neuronal growth and differentiation. To this purpose, we exploit a range of materials and fabrication techniques, to realize nanostructured superhydrophobic substrates, poly-e-caprolactone devices, surface chemical patterning and organic photovoltaic polymers. These research lines all belong to EU-funded projects, in collaboration with, amongst other groups, Dr. E. di Fabrizio (IIT, Genova and Kaust University, Saudi Arabia), Dr. F. Brandi (IIT Genova and CNR Pisa) and Dr. L. Ballerini (University of Trieste and SISSA, Trieste).
We are part of the European graphene flagship, as well as of the IIT graphene labs. In collaboration with other research groups in the flagship and in the IIT network, we are undertaking a number of approaches to engineer graphene-based biocompatible neural interfaces. We evaluate the biocompatibility of this material with the survival and growth of various cell lines and primary neurons. Moreover, electrophysiology combined with live cell imaging are exploited to characterize the functional properties of neural networks on graphene.
1. Scholz-Starke J* and Cesca F*: Stepping out of the shade: control of neuronal activity by the scaffold protein Kidins220/ARMS. Front Cel. Neurosci. 2016, 10:68. doi:10.3389/fncel.2016.00068 *corresponding authors
2. Paonessa F, Criscuolo S, Sacchetti S, Amoroso D, Scarongella H, Pecoraro Bisogni F, Carminati E, Pruzzo G, Maragliano L, Cesca F*, Benfenati F*: Regulation of neural gene transcription by optogenetic inhibition of the RE1-Silencing Transcription Factor. Proc Natl Acad Sci U S A. 2016 Jan 5;113(1):E91-E100. doi: 10.1073/pnas.1507355112. Epub 2015 Dec 23. *equal contribution
3. Piepgras J, Höltje M, Otto C, Harms H, Satapathy A, Cesca F, Benfenati F, Gitler D, Pich A, Zander J-F, Ahnert-Hilger G, Ruprecht K: Intrathecal immunoglobulin A and G antibodies to synapsin in a patient with limbic encephalitis. Neurol Neuroimmunol Neuroinflamm. 2015 Nov 4;2(6):e169. doi: 10.1212/NXI.0000000000000169. eCollection 2015 Dec.
4. Fiala GJ, Janowska I, Prutek F, Hobeika E, Satapathy A, Sprenger A, Plum T, Seidl M, Dengjel J, Reth M, Cesca F, Brummer T, Minguet S, Schamel WW: Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation. J Exp Med. 2015 Aug 31. pii: jem.20141271
5. Cesca F*, Satapathy A, Ferrea E, Nieus T, Benfenati F and Scholz-Starke J*: Functional Interaction between the Scaffold Protein Kidins220/ ARMS and Neuronal Voltage-Gated Na+ Channels. J Biol Chem. 2015 Jul 17;290(29):18045-55. doi: 10.1074/jbc.M115.654699 *corresponding authors
6. Cesca F*, Limongi T*, Accardo A, Rocchi A, Orlando M, Shalabaeva V, Di Fabrizio E and Benfenati F: Fabrication of biocompatible free-standing nanopatterned films for primary neuronal cultures. RSC Adv. 2014, 4(86), 45696-45702 *equal contribution
7. De Faveri S, Maggiolini E, Miele E, De Angelis F, Cesca F, Benfenati F and Fadiga L: Bio-inspired hybrid microelectrodes. A hybrid solution to improve long-term performance of chronic intracortical implants. Front Neuroeng. 2014 Apr 10;7:7
8. Cesca F*, Schiavo G and Benfenati F: Novel Experimental Models to Study Neurotrophin function. Eur J Neurodeg Dis. 2013 Vol 2; n. 2-3:89-99 *corresponding author
9. Lignani G, Raimondi A, Ferrea E, Rocchi A, Paonessa F, Cesca F, Tkatch T, Valtorta F, Cossette P, Baldelli P and Benfenati F: Epileptogenic Q555X SYN1 mutant triggers imbalances in release dynamics and short-term plasticity. Hum Mol Gen. 2013 Jun 1;22(11):2186-99
10. Medrihan L, Cesca F, Raimondi A, Lignani G, Baldelli P and Benfenati F: Synapsin II desynchronizes neurotransmitter release at inhibitory synapses by interacting with presynaptic calcium channels. Nat Commun. 2013;4:1512
11. Paonessa F, Latifi S, Scarongella E, Cesca F* and Benfenati F*: Specificity Protein 1 (Sp1)-dependent activation of the synapsin I gene (SYN1) is modulated by RE1-silencing transcription factor (REST) and 5’-Cytosine-Phosphoguanine (CpG) methylation. J Biol Chem. 2013 Feb 1;288(5):3227-39. *equal contribution
12. Limongi T*, Cesca F*, Gentile F, Marotta R, Ruffilli R, Barberis A, Dal Maschio M, Petrini EM, Santoriello S, Benfenati F and Di Fabrizio E: Nanostructured Superhydrophobic Substrates Trigger the Development of 3D Neuronal Networks. Small. 2012 Oct 2. doi: 10.1002/smll.201201377 *equal contribution
13. Scholz-Starke J, Cesca F, Schiavo G, Benfenati F and Baldelli P: Kidins220/ARMS is a novel modulator of short-term synaptic plasticity in hippocampal GABAergic neurons. PLoS One. 2012;7(4):e35785
14. Neubrand VE*, Cesca F*, Benfenati F and Schiavo G: Kidins220/ARMS as functional mediator of multiple receptor signalling pathways. J Cell Sci. 2012 Apr 15;125(Pt 8):1845-54 *equal contribution
15. Farisello P, Boido D, Nieus T, Medrihan L, Cesca F, Valtorta F, Baldelli P and Benfenati F: Synaptic and extrasynaptic origin of the excitation/inhibition imbalance in the hippocampus of synapsin I/II/III knockout mice. Cereb Cortex. 2013 Mar;23(3):581-93
16. Cesca F*#, Yabe A*, Spencer-Dene B, Scholz-Starke J, Medrihan L, Maden CH, Gerhardt H, Orriss IR, Baldelli P, Al-Qatari M, Koltzenburg M, Adams RH, Benfenati F and Schiavo G: Kidins220/ARMS mediates the integration of the neurotrophin and VEGF pathways in the vascular and nervous systems. Cell Death Differ. 2012 Feb;19(2):194-208 #corresponding author
17. Cesca F*#, Yabe A*, Spencer-Dene B, Arrigoni A, Al-Qatari M, Henderson D, Phillips H, Koltzenburg M, Benfenati F and Schiavo G: Kidins220/ARMS is an essential modulator of cardiovascular and nervous system development. Cell Death Dis. 2011 Nov 3;2:e226 #corresponding author
18. Wang S, Cesca F, Loers G, Schweizer M, Buck F, Benfenati F, Schachner M and Kleene R: Synapsin I is an oligomannose-carrying glycoprotein, acts as an oligomannose-binding lectin and promotes neurite outgrowth and neuronal survival when released via glia-derived exosomes. J Neurosci. 2011 May 18;31(20):7275-7290
19. Boido D, Farisello P, Cesca F, Ferrea E, Valtorta F, Benfenati F and Baldelli P: Cortico-hippocampal hyperexcitability in synapsin I/II/III knockout mice: age-dependency and response to the antiepileptic drug levetiracetam. Neuroscience. 2010 Nov 24;171(1):268-83.
20. Cesca F, Baldelli P, Valtorta F and Benfenati F: The synapsins: Key actors of synapse function and plasticity. Prog Neurobiol. 2010 Aug;91(4):313-48. Review.
21. Bracale A*, Cesca F*, Neubrand V, Newsome T, Way M and Schiavo G: Kidins220/ARMS is transported by a Kinesin-1-based mechanism likely to be involved in neuronal differentiation. Mol Biol Cell. 2007 Jan;18(1):142-52 *equal contribution
Principal Investigator in the following project:
Co-investigator in the following projects:
External Consultant in the following project:
Co-investigator in the following European Projects: