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Frank L. Margolis, PhD

Academic Title:

Professor Emeritus

Primary Appointment:

Neurobiology

Secondary Appointment(s):

Psychiatry

Additional Title:

Professor Emeritus

Email:

fmargolis@som.umaryland.edu flmomp@gmail.com

Location:

HSFII, S203-D

Phone (Primary):

(410) 706-8913

Phone (Secondary):

(410) 961-7351

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Education and Training

  • Antioch College, Yellow Springs, OH, 1954-1959, B.S. Chemistry
  • Columbia U., New York City, NY, 1959-1964, Ph.D. Biochemistry
  • Columbia U., New York City, NY, 1964-1965, Postdoctorate, Biochem.
  • Lab de Physiologie Comp, Universite de Paris, 1965-1966, Postdoctorate, Fetal endocrinology

Biosketch

The olfactory marker protein (OMP) was discovered by my laboratory many years ago. We showed that expression of this protein is virtually exclusively restricted to mature olfactory sensory neurons that are responsible for the sense of smell. The primary amino acid sequence of OMP was determined to be 50% identical in all vertebrate species, absent from invertebrates, and devoid of any sequence motifs that could give a hint as to function. To address function we generated knock-out animals and characterized the phenotype of these mice to obtain insight to function. OMP clearly plays a role in olfaction as demonstrated by behavioral analyses illustrating that its absence results in the need for a 50-100 fold higher concentration of odorant needed for behavioral response. In addition, analyses by voltage sensitive dyes illustrated that the OMP-KO mice were compromised in their response to odorants. Proof of function was further demonstrated by rescue of the OMP-KO phenotype by infection of the olfactory neurons with an OMP expressing adenovirus. To address mechanism, studies in my lab have continued in several directions:1-determination of the 3-D solution structure of OMP, 2-analysis of the role of OMP in Ca kinetics following odor stimulation and 3-identification of a protein binding partner. Our Ca imaging studies of the OMP-KO mice implicated Na/Ca-exchanger (NCX) activity was compromised in OMP-KO mice.

The 3-D structure of OMP has a beta-clam structure with an omega loop predictive of protein–protein interaction. Search for a protein partner led to the discovery of the interaction of OMP with the Bex1 and Bex2 proteins. Unlike OMP, these partner proteins have several active motifs including the ability to bind Ca/CaM. These studies have led us to the hypothesis that OMP is involved in regulating Ca kinetics in mature olfactory neurons. That observation, coupled with the olfactory behavioral deficit observed in the Bex1-KO mice, supported the hypothesis that OMP and Bex1 interacted to form a complex that regulated the participation of Ca/CaM in olfactory transduction. Further we proposed that Ca/CaM is a regulator of NCX activity and that the interaction of OMP/Bex/CaM is a regulatory triad that influences CaM availability to various steps in the olfactory transduction cascade. OMP does indeed bind to several Ca/CaM binding motifs in several proteins involved in olfactory transduction consistent with the hypothesis that OMP is a modulator of Ca/CaM activity or of other proteins that influence Ca availability in the cell. Thus, my expertise in olfactory function, protein-protein interaction, and role of regulators of NCX activity provide compelling reasons for my participation as a mentor on this grant proposal.

Research/Clinical Keywords

Chemosensory, olfaction, gene regulation,

Highlighted Publications

Koo JH, Smiley M, Lovering R and Margolis FL: Bex1 knock out mice show altered skeletal muscle regeneration Biochem Biophys Res Comm 363 pp 405-410 (2007)

Bettini E. and Margolis FL. Expression of an intron containing beta-tubulin mRNA in catfish olfactory epithelium J. Molec Histol. 38:571-579(2007).

Pyrski M, Koo JH, Polumuri S, Ruknudin A, Margolis JW, Schulze DH and Margolis FL Sodium-calcium exchanger expression in the mouse and rat olfactory systems J Comp Neurol 501:944-958 (2007).

Koo JH and Margolis FL: Bex1 knock out mice show altered skeletal muscle regeneration Biochem Biophys Res Comm 363 pp 405-410 (2007)

Reisert J, Yau KW Margolis FL Olfactory marker protein modulates the cAMP kinetics of the odour-induced response in cilia of mouse olfactory receptor neurons J.Physiol 585: 731-740 (2007).

Additional Publication Citations

Research Interests

Awards and Affiliations

Grants and Contracts

Professional Activity

Lab Techniques and Equipment

Selected Peer Reviewed Publications

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