Project Title: The Secret Dance of Parkinson’s Disease: Insights into the Interplay Between LRRK2 and Microtubules
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease and the most common movement disorder. It is linked to dominant missense mutations in leucine-rich repeat kinase 2 (LRRK2), yet our understanding of how LRRK2 causes neurodegeneration remains limited. Our multidisciplinary project aims at investigating LRRK2-dependent neurodegeneration by studying its conformational organization on microtubules by combining state-of-the-art computational methods with cryo-electron tomography (cryo-ET), hydrogen-deuterium exchange mass spectrometry (HDXMS), mutagenesis and cross-linking data into an integrative modeling approach.
Mentors: Drs. J. Andrew McCammon and Elizabeth Villa, UC San Diego
Project Title: Influenza Virulence and Transmissibility through the Computational Microscope
My work embraces a multiscale computational protocol that exploits different methods (Molecular Dynamics, Brownian Dynamics), analyses algorithms (Markov state model, PCA) and modeling tools for crossing the spatial scales (from molecular to subcellular / cellular) and exploring events occurring in different temporal scales. I will apply this computational approach to build a model of the entire influenza A (H1N1) virion, with all the surface components revealed and treated for the first time at atomic-level of detail. Unprecedented all-atom simulations of this realistic ~160 million-atoms model will serve to shed light on the Influenza A virus biology, virulence and transmissibility, with a particular emphasis on the role played by the glycans exposed by the neuraminidase and hemagglutinin glycoproteins.
Mentors: Dr. Rommie Amaro, UC San Diego; Dr. Ian Wilson, TSRI
Project Title: Cryo-Electron Tomography of the 3D Genome in situ Using V(D)J Recombination as the Model
The 3D architecture of the genome (3D genome) plays pivotal roles in gene expression and regulation. Despite its importance, the molecular organization of the genome remains one of the biggest unexplored frontiers in Biology. I plan to use cryo-electron microscopy, in its modality of cryo-electron tomography, to image intact molecular landscapes in 3-D which is uniquely suited to unveil molecular networks that organize the 3D genome.
Mentors: Drs. Elizabeth Villa and Cornelis Murre, UC San Diego