Areas of Interest
Our cells—like all eukaryotic cells—contain more than a dozen types of membrane-encapsulated compartments, called organelles, that perform specific jobs to maintain cell health and function. In the Mosalaganti lab, we investigate one of these organelle types, the lysosome, and its roles in human health and disease.
Lysosomes were initially thought to primarily serve a role in "waste management," degrading and recycling unwanted or damaged components within the cell. More recent research has shown that these organelles perform a plethora of cellular functions, most importantly in integrating a variety of different environmental and physiological signals.
Lysosomes are now considered a decision-making center controlling cellular growth and survival. Their function is highly dependent on proper positioning within the cell, as well as on their ability to coordinate activity with other organelles. Malfunctioning lysosomes play a role in a wide range of diseases, including cancer and cardiovascular disorders.
Our primary goal is to provide structural snapshots of how lysosomes perform their functions, how they get repaired when damaged, and how they communicate with other organelles to maintain cellular fitness. We are particularly interested in visualizing the distinct stages of lysosomal function within the cellular environment at unprecedented spatial resolution. These studies will reveal how mutations in lysosomal pathways lead to loss of function, reduced cellular viability, and, consequently, disease.
To achieve this goal, we combine state-of-the-art cryo-electron tomography approaches with biochemical and cell biological methods.
AI-based structure prediction empowers integrative structural analysis of human nuclear pores.
Mosalaganti S, Obarska-Kosinska A, Siggel M, Taniguchi R, Turoňová B, Zimmerli CE, Buczak K, Schmidt FH, Margiotta E, Mackmull MT, Hagen WJH, Hummer G, Kosinski J, Beck M.
Science. 2022; 376: eabm9506.
3D super-resolution fluorescence microscopy maps the variable molecular architecture of the Nuclear Pore Complex.
Sabinina VJ, Hossain MJ, Hériché JK, Hoess P, Nijmeijer B, Mosalaganti S, Kueblbeck M, Callegari A, Szymborska A, Beck M, Ries J, Ellenberg J.
Mol Biol Cell. 2021; 32: 1523–33.
In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges.
Turoňová B, Sikora M, Schürmann C, Hagen WJH, Welsch S, Blanc FEC, von Bülow S, Gecht M, Bagola K, Hörner C, van Zandbergen G, Landry J, de Azevedo NTD, Mosalaganti S, Schwarz A, Covino R, Mühlebach MD, Hummer G, Krijnse Locker J, Beck M.
Science. 2020; 370: 203–8.
Structural impact of K63 ubiquitin on yeast translocating ribosomes under oxidative stress.
Zhou Y, Kastritis PL, Dougherty SE, Bouvette J, Hsu AL, Burbaum L, Mosalaganti S, Pfeffer S, Hagen WJH, Förster F, Borgnia MJ, Vogel C, Beck M, Bartesaghi A, Silva GM.
Proc Natl Acad Sci U S A. 2020; 117: 22157–66.
Benchmarking tomographic acquisition schemes for high-resolution structural biology.
Turoňová B, Hagen WJH, Obr M, Mosalaganti S, Beugelink JW, Zimmerli CE, Kräusslich HG, Beck M.
Nat Commun. 2020; 11: 876.
Selective autophagy degrades nuclear pore complexes.
Lee CW, Wilfling F, Ronchi P, Allegretti M, Mosalaganti S, Jentsch S, Beck M, Pfander B.
Nat Cell Biol. 2020; 22: 159–66.
From the resolution revolution to evolution: structural insights into the evolutionary relationships between vesicle coats and the nuclear pore.
Beck M, Mosalaganti S, Kosinski J.
Curr Opin Struct Biol. 2018; 52: 32–40.
In situ architecture of the algal nuclear pore complex.
Mosalaganti S, Kosinski J, Albert S, Schaffer M, Strenkert D, Salomé PA, Merchant SS, Plitzko JM, Baumeister W, Engel BD, Beck M.
Nat Commun. 2018; 9: 2361.
For a list of publications from MyNCBI, click HERE