Research Experience

My Current Postdoc Project:

I am working as a postdoc at Dr. Alessandra Magistrato’s Lab at CNR-IOM, SISSA, Trieste, Italy. Currently I am working on SF3B1 protein which is part of the human spliceosome (SPL), is entailed in the recognition of a key pre-mRNA signalling sequence (branch point sequence (BPS)) and is the most frequently mutated SPL protein. Indeed, its cancer-associated mutations cause aberrant splicing by altering the BPS selection. The N-terminal of SF3B1 which is an intrinsically disordered region (IDR), undergoes phosphorylation of SF3B1 at its NTD (NTD-SF3B1) regulates splicing. I am using All-atom and coarse grained molecular dynamics (MD) simulations to elucidate the proteins' mechanisms by dissecting the functional and regulatory role of their IDRs. The computational predictions will be validated using NMR and bioSAXS with collaboration with Prof. Roberta Pierattelli and Prof. Isabella C. Felli from CERM, University of Florence, Italy and Prof. Silvia Onesti from Elettra Synchrotron, Trieste, Italy.

Details in the link bellow:

https://sites.google.com/view/idp-spl/home

My Ph.D. Work:

I did my Ph.D. from the Central European Institute of Technology, Masaryk University, Brno, Czech Republic. My Ph.D. research was mainly focused on computational predictions of protein conformational changes and their interaction properties possibly relevant in neurodegenerative diseases. 

• In the first project, I studied how multiple phosphorylation affects the conformational changes of the tau(210-240) fragment, a well-known IDP responsible for Alzheimer's disease. Using all atom MD simulation and validating the trajectories using NMR experimental parameters such as chemical shifts and 3JHN-H (provided by our collaborator Prof. Isabelle Landrieu, CNRS, France), I published as joint first author (Lasorsa A et al. 2023). 

• Further, I checked how multiple phosphorylation modulates the binding of the tau(210-220) fragment with 14- 3-3 protein using equilibrium and enhanced sampling (well-tempered metadynamics) and validated the results with ITC experiments. The manuscript is under preparation with my first authorship. 

• In the third project, I investigated the impact of multiple phosphorylation events (pS19, pS40) on the binding of the regulatory domain of human tyrosine hydroxylase (a rate-limiting enzyme in dopamine biosynthesis), which is a well- known IDR, with the 14-3-3ζ protein. This study utilized molecular dynamics (MD) simulations, and the findings were validated through bioSAXS, HDX-MS, NMR, and ITC experiments. The manuscript is under preparation as my joint first authorship. 

• In the fourth project, I screened FDA-approved drugs using high- throughput virtual screening followed by MD simulation to find the drugs modulating the dimer formation of 14-3-3 and the computational predictions were validated the prediction using nanoDSF measuring the melting temperature (Tm value). My colleagues are carrying out other experimental work (ITC, FRET and NMR) and it will be communicate as my first authorship. 

• In the fifth project, I simulated the CRABP I protein and checked how different molecular weights and concentrations of PEG affect urea-mediated unfolding and refolding. Various spectroscopy experiments support all these simulation results, and I have published two co-author research article, and another one research articles are under preparation as my co-authorship. 

• In the sixth project, I screened the NPATLAS database containing natural compounds (~32,000) against the EcR protein of B. tabaci using high-throughput virtual screening. I performed equilibrium MD simulations followed by SMD and umbrella sampling to identify possible lead molecules for potential insecticide development. This manuscript now under review with my corresponding and first authorship. 

• In the last project, during COVID- 19, I published one solo author and one first-author research article. I performed molecular docking and MD simulations of FDA-approved antivirals and COVID-19 proteases. 

• I have collaborated with Prof. Václav Brázda, Institute of Biophysics, Brno, Czech Republic, who is also my wife's PhD supervisor. They study interactions of G-quadruplex DNA and nanobodies using various experimental methods such as NMR, ITC, CD, EMSA, etc. I am trying to see the molecular-level interactions using enhanced sampling methods.