Research Biomolecular Sciences

Research

The Lagalwar Molecular Neurodegeneration lab uses cultured cell and mice models of Spinocerebellar ataxia type 1 (SCA1) to study the common mechanisms of neurodegenerative disease. SCA1, an autosomal dominant disease of the cerebellum and brainstem, begins with balance and motor deficits which are progressive and ultimately fatal. Similar to Alzheimer’s, Parkinson’s, Huntington’s and Prion disease, the cause of SCA1 is the abhorrent interactions and propagation of pathogenic proteins.

Our lab is interested in the following research questions:

• Does the mutant SCA1 protein ataxin-1 directly interact with mitochondrial proteins?
• Does mitochondrial dysfunction play an early role in the disease process?
• Do the recently discovered modes of propagation, namely tunneling nanotubes and
  exosomal release, occur in SCA1?

Our goals are to identify the common mechanisms by which neurodegenerative disease progresses and target these mechanisms with therapeutics.

Research

Several transition metals are essential for life as trace elements. These metal ions are found as cofactor in enzymes and are necessary for their proper function, e.g., nickel in hydrogenases, zinc in polymerases, and iron and copper in redox enzymes. For other transition metals, like silver, no biological function is known. However, if the concentration of these metals exceeds a certain level, all of them, independent from whether they are essential, are toxic. For this, organisms have to regulate their internal metal concentration tightly.

My research concentrates on different aspects of microbial metal homoeostasis:

• Mechanism of copper and silver resistance in Escherichia coli; and
• Influence of zinc on pathogenicity of Salmonella typhimurium.

Research

Our research interests emphasize the general area of structural biochemistry, using biophysical and biochemical approaches to characterize proteins involved in reversible phosphorylation of carbohydrates. We are particularly interested in understanding the molecular mechanisms by which glucan phosphatase Starch Excess4 regulate starch
phosphorylation in plant systems. Starch Excess4 is essential for starch degradation and its absence leads to accumulation of starch granules in plant leaves. Current studies focus on unraveling the mechanistic details of position-specific activity of Starch Excess4. One of the major challenges of studying Starch Excess4 is defining it in the complex starch structure.

Focusing on specific starch engagement and activity, students in my group will employ a variety of biophysical techniques including x-ray crystallography, small angle x-ray scattering, and differential scanning fluorimetry to study Starch Excess4. Our goal is to remove the key gaps in knowledge in reversible starch phosphorylation with the hope of developing a new strategy to utilize starch in an industrial setting and future biofuel research.

Research

In general, we are interested in understanding how microbes prepare amino acids for use in protein synthesis, in particular for the amino acid asparagine, which lays the foundation for the development of novel antibiotics. The process of preparing amino acids for protein synthesis requires attaching it to the adaptor molecule, transfer RNA (tRNA) catalyzed by the group of enzymes known as aminoacyl-tRNA synthetases. Life has evolved two distinct routes to attach asparagine to tRNA. We are also studying how to apply that understanding to expand the genetic code to create tools to better study diseases like Alzheimer’s and develop anti- cancer agents. Student collaborators learn not only biochemical techniques but also those in microbiology and molecular biology. The laboratory is in the Chemistry Department at Skidmore College and is affiliated with the RNA Institute at SUNY Albany.

In particular, we are interested in:

• Why certain bacteria, including some human pathogens, encode in their genomes more than one route to prepare the amino acid asparagine. We hypothesize that by having both routes, the bacteria are able to better handle environmental stresses and live in a wider range of conditions, including on us.
• Evolution of the bacterial aminoacyl-tRNA synthetases. We are studying how certain
  aminoacyl-tRNA synthetases evolved to recognize specific tRNA molecules in cells.
• Expanding the genetic code with pyroglumate to better study proteins like amyloid beta-peptides associated with Alzheimer’s disease and the anti-cancer agent, onconase.