Current CBI Trainees

Rachel Anderson 

Chemistry and Biochemistry
Alexis Komor Lab

CBI Appointment Period: 2022-23

Investigating adenine base editing mechanisms via fluorescence-based CRISPRi screens

Adenine base editors function via adenosine deamination to yield inosine, facilitating the conversion of A•T base pairs to G•C. This has powerful applications, however research regarding the mechanisms, intermediates, and cellular repair pathways involved in adenine base editing is lacking and prevents the application of ABEs as successful therapeutics and tools. To address this, CRISPRi screens couple fluorescence-based reporters with the inhibition of DNA repair genes to identify genes involved in inosine repair processing and provide insight into base editing mechanisms.

Benjamin Cordova

Chemistry and Biochemistry
Navtej Toor Lab

CBI Appointment Period: 2022-23
* San Diego Fellowship Recipient

Engineering protein-protein interactions in algal fatty acid biosynthesisChemical Modification of RNA by PEG makes RNA amenable to cryo-EM

RNA is not very amenable to cryo-EM analysis and these difficulties are due to the following barriers: RNA is sensitive to denaturation at the air-water interface in frozen cryo-EM grids, RNA adopts a preferred orientation in a thin layer of ice that limits resolution and RNA tends to aggregate in vitrified ice. To solve these problems, I used sulfinate chemistry to attach PEG on the surface of the RNA to prevent aggregation and shield the RNA from the damaging air-water interface to capture high-resolution structures of multiple
biologically significant RNAs constructs that lack any structural data.

Matthew Miyada

Chemistry and Biochemistry
Michael Burkart Lab

CBI Appointment Period: 2022-23

Solvatochromic Fluorescent Probes for Biosynthetic Gene Cluster Discovery

Marine organisms such as sponges and nudibranchs have been shown to harbor microbiomes of significant biodiversity. Critically, natural products isolated from these organisms and their microbiota have played an important role in the discovery of novel antibiotics. However, several marine holobionts and the diverse range of metabolites they produce remain unexplored. We plan to use synthase-selected single-cell genomics (SCG) to identify novel biosynthetic gene clusters (BGCs) within these microbiomes. Using established techniques, we are currently developing activity-based fluorescent probes to specifically target carrier-protein dependent synthases. Each probe consists of a solvatochromic fluorophore, reactive warhead, and linker. Upon in vivo uptake by microbial cells and attachment to their respective target enzymes, these probes exhibit changes in fluorescence intensity and emission wavelength, thereby allowing fluorescence-activated cell sorting (FACS) to isolate these cells and facilitate single-cell genomic analyses. Following the identification of unique BGCs, we hope to employ heterologous expression systems to produce novel natural products and assess their bioactivity..

Zulfiqar Mohamedshah

Chemistry and Biochemistry
Alexis Komor/Neal Devaraj Lab

CBI Appointment Period: 2022-23

Functionalization of DNA with Short Peptides through Site-Specific Enzymatic Modification

My research focuses on utilizing novel chemical and enzymatic approaches to develop an easy, site-specific
platform to modify genetic material with functional peptides for genetic engineering technologies. Specifically, I
am working to develop peptide substrates for tRNA guanine transglycosylase (TGT) to site specifically modify
DNA or RNA..

Adrian Wong

Chemistry and Biochemistry
Itay Budin Lab

CBI Appointment Period: 2022-23

Identifying the molecular modulators of membrane fluidity

Homeostatic regulation of cell membranes is tightly controlled in cells, but the underlying molecular mechanisms for sensing and regulating lipid composition remain undiscovered. The constitutive lipids that comprise cell membranes modulate their biophysical properties, such as their fluidity, which are critical for function. Alterations to plasma membrane fluidity have been shown to influence protein synthesis, cell-cell signaling, cell permeability, and endo- and exocytosis. Membrane fluidity responds to metabolic state and diet.
For instance, prolonged exposure of cells to excess saturated fatty acids decreases membrane fluidity and is a commonly used model for metabolic disorders such as obesity and type 2 diabetes. However, the mechanisms
cells use to counteract lipid-mediated metabolic changes on membrane fluidity remain poorly defined. The goal of my research project is to apply a systems biology approach to uncover the connection between cellular
metabolism and membrane fluidity to better understand how cells coordinate lipid homeostasis.