Research Interests

My research focusses on developing new experimental tools and predictive computational methods for probing and understanding the behaviour of biological molecules and systems, in particular proteins. Proteins are the executive molecules of life that through highly integrated and tightly regulated interactions set the molecular basis of our well-being. Yet the diverse and dynamic nature of proteins has made it challenging to devise methods that could be effectively used for thoroughly understanding the roles of proteins in human health and disease.


Rapid in-solution analysis of biomolecules and their interactions

During my PhD research, I devised platforms for probing dynamic heterogenous biomolecular interactions directly under their native conditions, in solution. A fundamental challenge associated with in-solution studies is the tendency of diffusion and random motion to oppose orderly analysis. Conventional approaches address this issue either by integrating matrices that keep molecules of similar properties together or perform analysis in gas phase. However, in both of these scenarios, it has remained challenging to fully preserve protein interactions and, moreover, matrix-based approaches limit the types of processes that can be studied to essentially static or slowly evolving ones.

To open up the possibility of probing biomolecular interactions on rapid, second time scale and directly in solution, I used a different strategy for controlling molecular motion: fabrication of micron scale structures in which fluids move in a laminar flow regime. Under such conditions, the chaotic mixing of molecules is suppressed even without the integration of physical barriers [1].

This strategy allowed me to create platforms that opened up new possibilities for in vitro studies of protein behaviour. Specifically, I used it for monitoring protein self-assembly in a high throughput label-free manner [2], for sizing and characterising proteins at unprecedented resolutions [3-4] and for probing interactions between self-assembled protein fibrils and their binding partners implicated in preventing pathological protein assembly and unfolding [5]. These developments required addressing core challenges in the field of micron scale separation science, such as effective integration of strong and stable electric fields with micron scale channels and the development of fabrication techniques that simultaneously provide high detection sensitivities and high resolution [6-7]. Together with collaborators, we have used these platforms for probing the amino acid content of proteins [8], for obtaining multidimensional fingerprints of proteins [9] and for purifying protein targets of interest from a complex cellular background [10]. We have also demonstrated the possibility to use these devices for probing interactions between self-assembled protein species and their binding partners implicated in the onset of neurodegenerative disorders, which had previously remained inaccessible due to the highly transient and heterogeneous nature of self-assembling protein mixtures [11].

Some of these approaches are currently being developed into products by Fluidic Ltd.



Exoelectrogenic behaviour of cells

I have also been using micron scale fabrication and flow engineering approaches for examining the exoelectrogenic behaviour of cells. Specifically, together with collaborators from the Howe group, we have built devices that have enabled us to probe the electrons that photosynthetic organisms secrete to the extracellular environment in response to sunlight. This concept lies at the heart of biological photovoltaic cells (BPVs) that by converting sunlight directly into electrical current provide as environmentally friendly and low-cost approach for harvesting solar energy. The micron scale BPV devices we recently demonstrated exceeded the power outputs of previously fabricated devices by a factor of five [12]. Read also the press release for this work.

Image credit: Nicola De Mitri.



Large scale multidimensional profiling

My current research efforts are predominantly focussed on developing tools for probe-free and explorative profiling of various complex biological mixtures, such as individual cells. I am using the high proccessive power of microfluidic and microdroplet platforms together with single-molecule spectroscopy and advanced data analysis approaches for achiving this goal.


Image credit: Gabriella Bocchetti, Department of Chemistry, University of Cambridge.



Research Supervising

I have worked closely together with a number of PhD and master's degree students and supervised the following theses:



Teaching

I have supervised Chemical Engineering undergraduate courses in "Process Calculations and Thermodynamics" and "Engineering Mathematics", and given seminars on topics closely related to my research, such as the use of microfluidics and micron scale analysis tools for biotechnological applications.