Nicholas Borotto

My research program strives to improve mass spectrometric-based detection and analysis of biomolecules. In particular, we pair mass spectrometry with chemical derivatization, photon irradiation, ion mobility, and radical chemistry to elucidate the three-dimensional structure of proteins, better characterize the acidic and hydrophobic proteome, detect and localize post-translational modifications. Centered at the interface of chemistry and biology, my research program provides students with the opportunity to tackle both biochemically-focused projects and biophysical questions at the core of the techniques themselves. Currently, my group is recruiting students for three projects:

1) Equipping a carbon monoxide laser to a mass spectrometer, characterizing the behavior of irradiated biomolecules, and applying infrared multiphoton dissociation (IRMPD) to instruments and at pressure regimes traditionally precluded from this technique.

2) Probing protein three-dimensional structure with photocaged small molecule reagents both in vitro and in vivo and demonstrating the utility of the temporal and spatial control that is provided by these probes.

3) Applying the tandem mass spectrometry technique free-radical initiated peptide sequencing (FRIPS) to complex mixtures of anions.

Lance Hellman

My research focuses primarily at probing the affects of amino acid perturbation on the overall tertiary structure. We use O6-alkylguanine-DNA alkyltranferase (AGT) as our model protein. AGT is a small DNA repair protein that remove alkylations on guanine and thymine residues. My lab uses structure guided design to alter the tertiary structure of AGT and measure the biothermodynamic affects of these mutations. We are interested in how these mutations affect the global stability of AGT by differential scanning fluorimetry. We also probe how these mutations affect AGT’s ability to bind in a cooperative manner by gel shift assays and fluorescence anisotropy techniques.

Edwin Oh

We are a research group that thrives on collaboration. Through our interactions with collaborators, public health labs, and patients we have developed a research program that interrogates the following themes:

1) Wastewater genomics and COVID-19

Wastewater testing has been used for years to investigate viral infections, to study illicit drug use, and to understand the socioeconomic status of a community based on its food consumption. While tools are in place in many states to evaluate the presence of specific viral strains, the community has not needed previously to collaborate on a global scale to standardize procedures to detect and manage COVID-19 transmission. In response to this challenge, our laboratories in Arizona, Nevada, and Washington have developed collection techniques and genomic and bioinformatic approaches to harmonize and visualize the impact of SARS-CoV-2 infection and viral mutation rates in communities populated by local citizens and international tourists. Our findings will contribute to the development of best practices in sampling and processing of wastewater samples and genomic techniques to sequence viral strains, an area required for environmental surveillance of infectious diseases, and has the strong potential to improve the clinically predictive impact of the viral genotype on patient care and vaccine utility.

2) Rare neurological conditions

An association between the 16p13.2 copy number variation deletion and seizures has suggested that a) systematic suppression of each of genes in the loci might yield similar neurological phenotypes seen in the 16p13.2 deletion; and b) such genes might be strong candidates for harboring rare pathogenic point mutations. Through these studies, we discovered USP7 as a message capable of inducing abnormal neurological activity in brain organoids, cultured neurons, and loss-of-function mouse models. Together with collaborators at the Foundation for USP7-Related Diseases (www.usp7.org), our studies are centered on the mechanism by which USP7 gene dosage and rare variants can induce pathology. In addition, we have also identified other gene loci that mimic USP7-related disorders in human and animal models.

3) Ciliary biology and neurodevelopmental conditions

Large-scale studies have begun to map the genetic architecture of Schizophrenia. We now know that the genetic contribution to this condition arises from a variety of lesions that include a) rare copy number variants (CNVs) of strong effect; b) common non-coding alleles of mild effect; and c) rare coding alleles that cluster in biological modules. The challenge that has emerged from these studies is the requirement for large sample sizes to detect significant genetic signals. These findings intimate that SZ is genetically heterogeneous and manifesting potentially as a clinically heterogeneous group of phenotypes with discrete physiological drivers. To address this challenge and to complement the ongoing sequencing effort of cross-sectional SZ, we propose to sample individuals with extreme phenotypes (i.e., resistant to treatment: TRS) to potentially discover an enrichment of causal rare variants which would have otherwise not been observed or been difficult to detect in a large, random sampling of SZ. In addition, we will focus on the role of a specific biological module, the pericentriolar material (including the centrosome, basal body, and primary cilium) and how it relates to the development of the brain and behavior through the genomic and functional dissection of PCM1.

Dylan Kosma

Dr. Dylan Kosma is a Plant Physiologist & Molecular Geneticist.  He is an Assistant Professor in the College of Agriculture, Biotechnology and Natural Resources, University of Nevada, Reno.

The aerial organs of all higher plants are covered with a lipid-rich cuticle that serves to protect plants from their environment. The cuticle is comprised of a lipid polymer, cutin, that is embedded and covered with aliphatic waxes. Suberin is a biosynthetically-related lipid polymer that is found in tree bark, seed coats, the surface of mature roots and surrounding the vasculature of young roots. Suberin production is a ubiquitous response to wounding. Collectively, cutin and suberin comprise the most abundant, naturally occurring lipid polymers on the planet. It is estimated that leaf cuticles alone represent a surface area twice that of the earth’s land surface.

The Kosma lab is focused on understanding the complex plant lipid polymers cutin and suberin. We use a multidisciplinary approach combining biochemistry, analytical techniques and molecular genetics to comprehend the macromolecular structure and functional significance of these polymers with an emphasis on their role in plant tolerance to abiotic stress.