Velia Siciliano

Velia Siciliano
Istituto Italiano di Tecnologia | IIT · Center for Advanced Biomaterials for Healthcare

Group Leader. Istituto Italiano di Tecnologia-IIT

About

41
Publications
7,825
Reads
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875
Citations
Additional affiliations
July 2012 - present
Massachusetts Institute of Technology
Position
  • PostDoc Position
Description
  • Engineering of protein-based in vivo biosensor in mammalian cells. microRNA based cell classifiers. Engineering of orthogonal elements for regulation of gene expression in mammalian cells.
January 2012 - present
Università degli Studi di Napoli Federico II
August 2007 - December 2011
Telethon Institute of Genetics and Medicine
Position
  • PhD Student
Description
  • Construction and characterization of a microRNA based synthetic oscillator in mammalian cells.
Education
September 2004 - September 2006
University of Naples Federico II
Field of study
  • Medical Biotechnology
September 2001 - October 2004
University of Naples Federico II
Field of study
  • Health Biotechnology

Publications

Publications (41)
Article
Full-text available
Synthetic networks require complex intertwined genetic regulation often relying on transcriptional activation or repression of target genes. CRISPRi-based transcription factors facilitate the programmable modulation of endogenous or synthetic promoter activity and the process can be optimised by using software to select appropriate gRNAs and limit...
Chapter
Synthetic biology has enabled innovative approaches in many different fields, spanning from industry to biopharmaceutics to biomedicine. In the latter, advances in bioengineering technologies have made possible the development of new therapies which are at the forefront of treatments for hard-to-cure diseases. In this chapter, we will focus on cell...
Article
Full-text available
Scientific collaborations among nations to address common problems and to build international partnerships as part of science diplomacy is a well-established notion. The international flow of people and ideas has played an important role in the advancement of the ‘Sciences’ and the current pandemic scenario has drawn attention towards the genuine n...
Article
The ability to reprogram mammalian cells with tight spatiotemporal control over gene expression and cell response has provided a powerful means to address biomedical challenges. To provide safer synthetic biology products, RNA has recently emerged as an alternative to DNA to deliver transgenes into mammalian cells. In this review, we discuss recent...
Article
Full-text available
Transient transfections are routinely used in basic and synthetic biology studies to unravel pathway regulation and to probe and characterise circuit designs. As each experiment has a component of intrinsic variability, reporter gene expression is usually normalized with co-delivered genes that act as transfection controls. Recent reports in mammal...
Preprint
Despite the failures to tackle early coordinated responses at national and multinational levels, the global emergence of Coronavirus Disease 2019 (COVID-19) pandemic promoted unprecedented actions on the science-policy, science-communication, and science-diplomacy interfaces worldwide. With varying degrees of success, various actions within the rea...
Chapter
Synthetic biology has been advancing cellular and molecular biology studies through the design of synthetic circuits capable to examine diverse endogenously or exogenously driven regulatory pathways. While early genetic devices were engineered to be insulated from intracellular crosstalk, more recently the need of achieving dynamic control of cellu...
Article
Full-text available
Engineered mammalian cells for medical purposes are becoming a clinically relevant reality thanks to advances in synthetic biology that allow enhanced reliability and safety of cell-based therapies. However, their application is still hampered by challenges including time-consuming design-and-test cycle iterations and costs. For example, in the fie...
Article
Full-text available
Synthetic biology has the potential to bring forth advanced genetic devices for applications in healthcare and biotechnology. However, accurately predicting the behavior of engineered genetic devices remains difficult due to lack of modularity, wherein a device's output does not depend only on its intended inputs but also on its context. One contri...
Article
Full-text available
Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of ot...
Article
Proteins can function as biomarkers of pathological conditions, such as neurodegenerative diseases, infections or metabolic syndromes. Engineering cells to sense and respond to these biomarkers may help the understanding of molecular mechanisms underlying pathologies, as well as to develop new cell-based therapies. While several systems that detect...
Article
The field of mammalian synthetic biology is expanding quickly, and technologies for engineering large synthetic gene circuits are increasingly accessible. However, for mammalian cell engineering, traditional tissue culture methods are slow and cumbersome, and are not suited for high-throughput characterization measurements. Here we have utilized ma...
Preprint
Full-text available
A significant goal of synthetic biology is to develop genetic devices for accurate and robust control of gene expression. Lack of modularity, wherein a device output does not depend uniquely on its intended inputs but also on its context, leads to poorly predictable device behavior. One contributor to lack of modularity is competition for shared li...
Preprint
Full-text available
Despite recent advances in genome engineering, the design of genetic circuits in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here we demonstrate that competition for limited transcriptional and translational resources dynamically couples otherwise independent co-expressed exogenous genes, leading to diminishe...
Article
3D vertical nanostructures have become one of the most significant methods for interfacing cells and the nanoscale and for accessing significant intracellular functionalities such as membrane potential. As this intracellular access can be induced by means of diverse cellular membrane poration mechanisms, it is important to investigate in detail the...
Article
Full-text available
The main aim of cell instructive materials (CIMs) is to guide in a controlled way cellular behaviour by fine-tuning cell-material crosstalk. In the last decades, several efforts have been spent in elucidating the relations between material cues and cellular fate at the nanoscale and in the development of novel strategies for gaining a superior cont...
Article
Synthetic biology aims to rewire cellular activities and functionality by implementing genetic circuits with high biocomputing capabilities. Recent efforts led to the development of smart sensing interfaces which integrate multiple inputs to activate desired outputs in a highly specific and sensitive manner. In this review, we highlight protein-bas...
Article
Synthetic biology aims to rewire cellular activities and functionality by implementing genetic circuits with high biocomputing capabilities. Recent efforts led to the development of smart sensing interfaces which integrate multiple inputs to activate desired outputs in a highly specific and sensitive manner. In this review, we highlight protein-bas...
Article
Full-text available
Synthetic Biology has enabled new approaches to several medical applications including the development of immunotherapies based on bioengineered cells, and most notably the engineering of T-cells with tumor-targeting receptors, the Chimeric Antigen Receptor (CAR)-T cells. CAR-T-cells have successfully treated blood tumors such as large B-cell lymph...
Article
Full-text available
The development of RNA-encoded regulatory circuits relying on RNA-binding proteins (RBPs) has enhanced the applicability and prospects of post-transcriptional synthetic network for reprogramming cellular functions. However, the construction of RNA-encoded multilayer networks is still limited by the availability of composable and orthogonal regulato...
Article
Full-text available
Understanding and reshaping cellular behaviors with synthetic gene networks requires the ability to sense and respond to changes in the intracellular environment. Intracellular proteins are involved in almost all cellular processes, and thus can provide important information about changes in cellular conditions such as infections, mutations, or dis...
Chapter
Recently developed DNA assembly methods have enabled the rapid and simultaneous assembly of multiple parts to create complex synthetic gene circuits. A number of groups have proposed the use of computationally designed orthogonal spacer sequences to guide the ordered assembly of parts using overlap-directed or homologous recombination-based methods...
Article
Synthetic regulatory circuits encoded in RNA rather than DNA could provide a means to control cell behavior while avoiding potentially harmful genomic integration in therapeutic applications. We create post-transcriptional circuits using RNA-binding proteins, which can be wired in a plug-and-play fashion to create networks of higher complexity. We...
Article
Prokaryotic regulatory proteins respond to diverse signals and represent a rich resource for building synthetic sensors and circuits. The TetR family contains >105 members that use a simple mechanism to respond to stimuli and bind to distinct DNA operators. We present a platform that enables the transfer of these regulators to mammalian cells, whic...
Article
Full-text available
miRNAs are small non-coding RNAs able to modulate target gene expression. It has been postulated that miRNAs confer robustness to biological processes, but clear experimental evidence is still missing. Here, using a synthetic biological approach, we demonstrate that microRNAs provide phenotypic robustness to transcriptional regulatory networks by b...
Article
Full-text available
The ongoing merge between engineering and biology has contributed to the emerging field of synthetic biology. The defining features of this new discipline are abstraction and standardisation of biological parts, decoupling between parts to prevent undesired cross-talking, and the application of quantitative modelling of synthetic genetic circuits i...
Article
Full-text available
Synthetic biology aims at designing and building new biological functions in living organisms. The complexity of cellular regulation (regulatory, metabolic, and signaling interactions, and their coordinated action) can be tackled via the development of quantitative mathematical models. These models are useful to test biological hypotheses and obser...
Article
Full-text available
We collected a massive and heterogeneous dataset of 20 255 gene expression profiles (GEPs) from a variety of human samples and experimental conditions, as well as 8895 GEPs from mouse samples. We developed a mutual information (MI) reverse-engineering approach to quantify the extent to which the mRNA levels of two genes are related to each other ac...
Article
Full-text available
Understanding the relationship between topology and dynamics of transcriptional regulatory networks in mammalian cells is essential to elucidate the biology of complex regulatory and signaling pathways. Here, we characterised, via a synthetic biology approach, a transcriptional positive feedback loop (PFL) by generating a clonal population of mamma...
Article
Regulation of gene expression is a carefully regulated phenomenon in the cell. “Reverse-engineering” algorithms try to reconstruct the regulatory interactions among genes from genome-scale measurements of gene expression profiles (microarrays). Mammalian cells express tens of thousands of genes; hence, hundreds of gene expression profiles are neces...
Article
Full-text available
RNA interference (RNAi) is a regulatory cellular process that controls post-transcriptional gene silencing. During RNAi double-stranded RNA (dsRNA) induces sequence-specific degradation of homologous mRNA via the generation of smaller dsRNA oligomers of length between 21-23nt (siRNAs). siRNAs are then loaded onto the RNA-Induced Silencing multiprot...
Data
Supplementary material for Modeling RNA interference in mammalian cells. Results and fitting of in vitro experiments on hamster ovary cell line (CHO) constitutively expressing tTA protein. We measured mRNA levels, by quantitative Real-Time PCR for a large range of concentrations of siRNA oligomers, from 0.001 pmol to 200 pmol (total concentration)....

Questions

Question (1)
Question
I have recently acquired a QiAgility, that should make the preparation of PCR plates automated, faster and more accurate. However, since we bought it, we have really poor experience with accuracy of pipetting. For example, if we want to get 4ul pipetted, we should have 15ul of dead volume, which is unreasonable if we think how much reagents for qPCR costs. Also the accuracy drops down along with decreasing volume of the master mix, meaning that the only first samples will work as fine as manual pipetting.
The technician from Qiagen, after coming few times concluded that the machine cannot give us what we need (pipetting few uls per well to run a qPCR).
Do you have experience with this machine?
Any feedback is much appreciated!

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Projects

Project (1)
Project
Combinatorial systems and synthetic biology approaches to characterise molecular mechanisms that drive T cell dysfunction