Biochemistry and Biophysics Division


Biochemistry and Biophysics consider the fundamental chemical principles that govern all biological systems. The Chemistry Department at UAlbany is home to an exciting multidisciplinary program in Biochemistry and Biophysics.

Particular areas of expertise are Biomolecular Structure & Function, Sensing and Imaging, Metallobiochemistry, RNA Biochemistry, Chemical Genetics, Bionanotechnology, Theory and Simulation, and Neurochemistry. Synthesis, characterization and mechanism of action of biological molecules are also important research activities. All of these areas of interests are related to both fundamental studies of biological macromolecules and human diseases, including cancer, diabetes, eye diseases, and neurological disorders such as Alzheimer’s diseases, ALS and epilepsy.

Biochemistry and Biophysics in the Department of Chemistry at UAlbany has a rich tradition of interdisciplinary interaction and success. Many other research groups that may belong to other Divisions in the Department also work at this dynamic boundary, and have a wide range of interdepartmental collaborations. Laboratory rotations allow graduate students to explore their individual areas of interest before choosing their research mentors. Whether you work in bioanalytical, bioorganic, or biophysical chemistry, you will belong to a vibrant community of dedicated researchers with the highest scientific aspirations.

Current activities in Biochemistry and Biophysics target:

Protein dynamics, kinetics and reactivity

The Pande lab investigates the alpha, beta and gamma crystallins in the eye lens. The alpha crystallins are ATP-independent molecular chaperones which form distinct assemblies with their client proteins. The crystallins are also subject to post-translational modifications (PTMs) which lead to pathology. Age-associated PTMs and chaperone-client assemblies are found not only in the lens but in many other tissues, including the brain and heart. The Pande group is involved in: 1) understanding the mechanistic bases of how PTMs (e.g., deamidation), lead to protein degradation, and 2) in determining the binding loci of the chaperone-substrate pair, the energetics of binding, and the client protein conformation in the bound state.

The Shekhtman lab uses state-of-the-art NMR spectroscopy to study how the biomolecular dynamics of the large family of mini-proteins, cyclic peptides or cyclotides, influences their binding to various protein targets. Most cyclic peptides are anti-microbial peptides and critical for the immune system of both plants and humans.

The Niu group is investigating the structure-function relationship of AMPA receptors, a subtype of glutamate ion channel receptors. AMPA receptors are exclusively expressed in the central nervous system and essential for brain development and function. For this study, the researchers in his lab do electrical current recording with single cells that express various subunits, isoforms and channel types. To adequately measure the kinetic rate constants of channel-opening induced by the binding of glutamate, an endogenous neurotransmitter, his group is using rapid kinetic techniques, including a laser-pulse photolysis technique and a “caged glutamate”.


Structure of proteins and protein complexes

An important aspect of understanding the mechanism of childhood genetic cataracts, is the determination of the structures of cataract-associated mutants. The Pande lab has published the first high-resolution x-ray crystal structure of human gammaD-crystallin and a one of its cataract-associated mutants. A recent collaboration (Prof. S. Sarma, Indian Institute of Sciences), has resulted in the 3D-structure of human gammaC crystallin using NMR. An ongoing collaboration with Prof. A. Shekhtman, has led to the identification of residue-specific changes in the structure of several gamma crystallin mutants, also using NMR.

Proteins play a central role in propagation and metabolism of a living cell. Three dimensional structure of proteins and their complexes are critical for unraveling protein function in health and disease. By using in-cell NMR spectroscopy, Dr. Shekhtman’s group is able to visualize proteins and their complexes at atomic resolution in live human and bacterial cell and used this technique to study protein-protein and protein-drugs interactions.

One of the challenges faced in RNA research is that function is often dictated by the precise 3-D structure the molecule chooses to adopt, but these structures are nearly impossible to obtain via conventional NMR or X-ray methods. The Chen lab is developing accurate computer simulations capable of folding RNA sequences into their preferred 3-D structure to facilitate structure-function studies of emerging RNAs of interest such as those from viral genomes.


Chemical genetics
Using chemical genetic approaches, we are working on several projects for the synthesis of new structures that mimic biological function (molecular recognition), and the design and synthesis of chemical reagents that probe and allow control of biological function (bioorganic and medicinal chemistry).

The Niu group uses a SELEX technique to find useful RNAs that target AMPA receptors. This is an in vitro evolution approach by which desired phenotypes (shapes of RNAs) are selected for tight molecular recognition and regulation of the receptor function. These RNAs are being also chemically modified to be stable, which will be amenable to be used as drug candidates.

The Shekhtman group designed a library of genetically encoded peptide aptamers, which are used as biologically active agents to study inhibition of various biological processes. The peptide library can be screened against its biological targets by using both yeast two-hybrid system as well as in-vitro and in-cell NMR spectroscopy.

The Chen lab is interested in understanding the principles of RNA-ligand interactions to design, in-silico, RNA aptamers incorporating modified nucleotides to enhance their intrinsic affinity and specificity for small-molecule analytes for diagnostic and biosensing applications.


Sensing and Imaging

Development of biomedical imaging agents and sensors has been new yet fast growing research area in the Department of Chemistry. Nanomaterials are ideal platforms for biosensor and imaging agent construction due to their unique physiochemical properties at the bio-nano interface. The Yigit Lab has been investigating two and three dimensional nanoparticles and highly programmable DNA nanotechnology for real life applications including but not limited to therapeutic and diagnostic nanodevice engineering, miRNA detection and heavy metal ion sensing.


Neurochemistry
Transmembrane proteins are a very important class of proteins. The function of these membrane proteins ranges from brain activities, such as memory and learning, to cancer as well as immune systems.

The Niu group studies glutamate ion channels using photochemical probes and develops novel agents such as RNA aptamers to regulate the function of these receptors. Small-molecules like 2,3-benzodiazepine compounds and RNA aptamers are potential drugs for a treatment of a number of neurological diseases such as stroke, ALS and epilepsy. Developing more potent and more selective inhibitors is the major goal of his study. In addition, his lab is also developing new RNA aptamers as a potent, water-soluble class of antagonists as drug candidates.

The Pande is conducting detailed investigations of the thermodynamic and structural aspects of the chaperone complexes of alphaB-crystallin with client proteins. The role of alphaB-crystallin in multiple sclerosis and in neuro-inflammation has been reported by several labs. The molecular chaperone properties of alphaB-crystallin are implicated in these roles and the Pande lab is addressing the molecular mechanism of the chaperone function.

The Shekhtman lab studies how the structure of the receptor for advanced glycation end products, RAGE, influences its biological activity, which, under pathological conditions, leads to the complications of diabetes, inflammation, and Alzheimer’s disease.


Biomaterial

The Niu lab is also working on a project in the development of RNA hydrogel. Hydrogel is a class of material formed by a hydrophilic polymer network with high water retention capacity. As a material, the property of a hydrogel, such as swelling, permeation, mechanical, optical and surface properties, can be modulated for various applications, such as tissue engineering scaffolds and drug delivery vehicles. RNA hydrogel is unique because all other types of biomolecules, such as lipids, peptides, proteins, polysaccharides, and DNA, but not RNA, have previously been found to form hydrogels.