Alok Shah Graduate Student University of Iowa Roy J and Lucille A Carver College of Medicine Department of Internal Medicine 500 EMRB Iowa City IA 5224 PHONE: 319 335 6540 FAX: 319 335 7623 alok-shah@uiowa.edu

Hometown: Mumbai, India
B.S. in Biological Chemistry, Grinnell College, 2004.
Department: Interdisciplinary Program in Molecular Biology, 2nd year.

I joined the Welsh Lab in the Fall 2005. I am interested in the role of Bardet-Biedl Syndrome (BBS) on moltile cilia structure and function in the lungs.

Bardet-Biedl Syndrome (BBS) is an autosomal recessive disorder with diverse phenotypes including obesity, retinopathy, polydactyly, hypogenitalism, renal abnormalities, developmental delay and an anecdotal increased incidence of asthma. Eight BBS genes have been identified (Bbs1-8), which have little or no structural similarity, but mutations in these genes cause similar disease phenotypes. Recent studies suggest that BBS genes are involved in the function of primary (non-motile) cilia. However, little is known about the function of
BBS proteins in motile cilia, such as those found on airway epithelial cells. Because some BBS proteins are expressed in airways and BBS patients may have an increase in asthma, we hypothesized that mice missing these BBS proteins would have abnormal airway cilia.

Using scanning electron microscopy, we found that the loss of BBS1, -2, -4 or -6 produced an abnormal structure in a small proportion of motile cilia in vitro and in vivo. The abnormalities were heterogeneous both for cilia on an individual cell and between cells. Loss of BBS2 disorganized the cellular
localization of acetylated alpha-tubulin in airway epithelia. We also observed increased apoptosis in Bbs2-/- and Bbs4-/- mice alveoli.

Our preliminary data suggest a small increase in inflammatory cytokines in Bbs4-/- mice in response to ovalbumin-induced allergic conditions, but not following LPS inhalation. But bronchoalveolar lavage cell counts and measurements of airway reactivity to methacholine challenge were not increased. The data suggest that the loss of BBS proteins produces some abnormal ciliary morphology in mouse lungs, however, the physiologic consequences remain uncertain. Understanding the role of BBS proteins in airway epithelia will
provide us with insight to the cellular mechanisms involved in ciliary structure and function and the role of BBS in lung disease.