Kevin Ryan teaches a variety of Biochemistry courses at The City College of  New  York (CCNY), and in the doctoral programs in Biochemistry and Chemistry at the City University of New York Graduate Center. 

 

Ryan lab Research- Current Projects

Molecular Recognition and Olfaction

We use techniques from medicinal chemistry and biochemistry to study the inner workings of the mammalian olfactory receptors. 

Molecular dynamics simulation of octanal, an odorant with several rotatable bonds. Our lab investigates how the mammalian odorant receptors recognize such conformationally mobile ligands.

 

 

The human genome encodes a subgroup of about 400  distinct G-protein coupled receptors (GPCRs) that are categorized by protein sequence homology as olfactory (or odorant) receptors. These receptors are expressed in the plasma membrane of olfactory sensory neurons in the olfactory epithelium. Each sensory neuron typically chooses to express one olfactory receptor family member per cell, and each receptor has its own pharmacology through which it contributes to the monitoring of volatile organic compounds (VOCs) in the environment. As of March 2019 there are no high resolution structures of any olfactory receptor. We study the interaction from the point of view of the odorant ligand, often using the rodent I7 aldehyde receptor as a receptor exemplar. We address such mysteries as: how does a receptor distinguish among organic functional groups? How can a flexible, hydrophobic carbon chain help to define the receptive range of a receptor (i.e. its unique pharmacology)? How does the number of receptors activated by an odorant vary with carbon chain flexibility? Does pharmacologic antagonism contribute to the “olfactory code?” What molecular features distinguish a GPCR agonist from antagonist?

 

Chemically Synthesized Expression Vectors for Small RNA

We are developing a synthetic DNA oligonucleotide expression platform for the expression of Small RNA in human cells. Our strategy does not involve plasmids, viral vectors or chemical RNA synthesis.

Small RNA, that is, RNA having fewer than about 200 nucleotides(nt), can do interesting things, like catalyze a chemical reaction, interfere with the expression of a particular gene, or guide a gene-editor like CRISPR to a single genomic site for repair or knockout. But compared to DNA, and on account of its 2’ OH group, RNA is labile, and its synthesis difficult and expensive. Obviously, synthetic DNA–chemically stable, inexpensive and easy to make–can carry the same sequence information as RNA, but how do you tell a cell to transcribe it? Transcription generally requires a promoter, and that means using a double-stranded DNA in the form of a plasmid (which can become integrated in an oncogene and result in cancer) or repurposed virus vector. We search for rare and unique DNA secondary structures, sequences and non-natural nucleotides that can allow us to the control site-specific transcription initiation and termination by human RNA Polymerase III.

Myodesopsia: Biochemical Analysis and Control

Vitreous floaters interfere with clear-sightedness; we study their biochemistry to provide a foundation for therapeutic development.

 The mammalian eye is filled with a clear gel composed mainly of hyaluronic acid and collagen. During aging, the gel can form light-obstructing structures that cast a shadow on the retina, and thereby interfere with normal vision. This condition is known as myodesopsia, or, more commonly, vitreous floaters. We study the finer details of vitreous floater structure and composition. Improvements in understanding floaters at the molecular-level will provide a basis for the search for a drug that can lead to their control, and possibly even their disintegration in oculus