Structure, folding and design of integral membrane proteins

What is the biophysical basis of transmembrane helix-helix interaction?

We are interested in investigating this process and in developing methods for predicting and designing oligomeric complexes of transmembrane helices.

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News
January 1, 2020
New Graduate Students Join the Lab!

The Senes Lab welcomes Tyler Peterson (Biophysics) and Samridhi Garg (Biochemistry) who just joined!

February 1, 2019
Good luck, Beth!

After three years as a postdoc in our lab, Elizabeth Caselle is leaving to work as a scientist at PPD, a leading global company in drug development services in Middleton WI. Congratulations for the job and good luck, Beth!

December 15, 2018
New graduate student joins the lab!

The Senes lab welcomes Joshua Choi (Biochemistry) who just joined!

December 12, 2018
Alessandro has been awarded the 2019 UWPA Postdoc Mentoring Award!

Alessandro was awarded the UW-Madison Postdoctoral Association Postdoc Mentoring Award, which recognizes advisors for "actively supporting postdoctoral mentoring in research, scholarship, career development, diversity and inclusion, and for having a great impact on postdoctoral growth, development, and training".

November 23, 2018
New publication: A software package to analyze photobleaching

Congratulations to Samson Condon for the publication of his latest paper in Methods! Sam collaborated with the Hoskins group and helped develop the software package AGATHA (A GATHering of Analyses) which is used to facilitate single-molecule TIRF microscopy analyses, including fitting photobleaching traces to a step function.

  • Kaur H, Jamalidinan F, Condon SGF, Senes A, Hoskins AA "Analysis of spliceosome dynamics by maximum likelihood fitting of dwell time distributions" Methods 2018 in press (DOI:10.1016/j.ymeth.2018.11.014) [PDF]
November 7, 2018
The Biochemistry Department recognizes our three Sams!

The three Sams in our lab were celebrated in an article on the Biochemistry web site:

"Shouting 'Sam' in the lab of University of Wisconsin–Madison biochemistry professor Alessandro Senes won't get you far. Three talented young scientists will turn their heads: Samantha Anderson, Samson Condon, and Samuel Craven."

See the full article here.

August 3, 2018
Students, Researchers Push Boundaries of Computational Biochemistry

"We investigate how proteins in the cell membrane come together to form complexes," associate professor of biochemistry Alessandro Senes explains. "We use molecular modeling tools to study something that is often very hard to do with conventional experimental structural methods."

See the full article here.

May 10, 2018
Gilbert Loiseau is awarded a CBI Predoctoral Traineeship

Gilbert is awarded a tranineeship with the Chemistry-Biology Interface training program. Gilbert is the first Senes lab graduate student to be selected for the training grant! His project focuses on modulating protein signaling using metals as ligands.

April 11, 2018
Congratulations fellowship recepients!

Congratulations to this year's Senes lab fellowship recepients! Graduate student Sam Condon was awarded the Arthur B. Michael Fellowship for the 2018-19 academic year and undergraduate student Collin McFadden was awarded the Wisconsin Hilldale Undergraduate/Faculty Research Fellowship.

December 19, 2017
New publication: CKX1 from Arabidopsis homooligomerizes via the GASright motif

Congratulations to Samantha Andereson for the publication of her latest paper in Plant Physiology! Sam collaborated with Tomas Werner's group and modeled the mechamism by which the membrane embedded cytokinin oxidase/dehydrogenase CKX1 homooligomerizes via the GASright motif.

  • Niemann MCE, Weber H, Hluska T, Leonte G, Anderson SM, Novak O, Senes A, and Werner T. "The cytokinin oxidase/dehydrogenase CKX1 is a membrane-bound protein requiring homooligomerization in the endoplasmic reticulum for its cellular activity." Plant Phys. 2018 176, 2024-39 [PDF]
December 15, 2017
New graduate student joins the lab!

The Senes lab welcomes Gilbert Loiseau (Biochemistry) who just joined!

December 13, 2017
New publication: structural organization of the transmembrane and coiled coil domains of the FtsLB complex


Congratulations to Sam Condon, Deena-Al Mahbuba, Claire Armstrong, Gladys Díaz-Vázquez, Sam Craven, Loren LaPointe and Rika Khadria and to our collaborators for the publication of their latest paper in JBC! The work applies a variety of bioinformatics, modeling, biophysical and biological experiments to investigate the structure and the function of this essential complex of the bacterial divisome.

  • Condon SGF*, Mahbuba DA*, Armstrong CR, Diaz-Vazquez G, Craven SJ, LaPointe LM, Khadria AS, Chadda R, Crooks JA, Rangarajan N, Weibel DB, Hoskins AA, Robertson JL, Cui Q, Senes A "The FtsLB sub-complex of the bacterial divisome is a tetramer with an uninterrupted FtsL helix linking the transmembrane and periplasmic regions" J. Biol. Chem. 2018 293, 1623-41 (*authors contributed equally) [PDF]
October 13, 2017
New publication: Cα-H···O=C hydrogen bonds contribute to stability the GASright motif

Congratulations to Samantha Anderson, Ben Mueller, and Evan Lange for the publication of their latest paper in JACS! They combined the power of computation and experimentation to analyze the forces that drive the association of an array of transmembrane dimers belonging to the common GASright structural motif. They found that hydrogen bonds in which the donor are Cα-H carbons, combined with van der Waals packing predict the stability of these GxxxG-mediated dimers in biological membranes. The finding provides experimental evidence that weak hydrogen bonds can drive the association of transmembrane helices.

  • Anderson SM*, Mueller BJ*, Lange EJ, Senes A. "Combination of Cα-H hydrogen bonds and van der Waals packing modulates the stability of GxxxG-mediated dimers in membranes" J Am Chem Soc. 2017 139, 15774-83 (*authors contributed equally) [PDF]
July 18, 2017
Congratulations and good luck Deena!

Deena has graduated with a Master's degree. During her time in the lab, Deena performed in vivo studies on the E. coli bacterial divisome proteins FtsB and FtsL. Deena is moving to the Massachusetts Institute of Technology to work in Laura Kiessling's lab.

July 18, 2017
Good luck, Claire!

After three years as a undergraduate and two years as a research intern, Claire Armstrong is moving to the University of Colorado at Boulder for graduate school.

April 3, 2017
Congratulations to our three Sams for earning fellowships!

Congratulations to fellowship recepients in the lab: graduate students Sam Anderson and Sam Craven were awarded the Dr. James Chieh-Hsia Mao Wisconsin Distinguished Graduate Fellowship, and Sam Condon the William R. & Dorothy E. Sullivan Wisconsin Distinguished Graduate Fellowship, for the 2017-18 academic year.

March 13, 2017
Sam Anderson is awarded a CIBM Predoctoral Traineeship

Sam is awarded a tranineeship with the Computation and Informatics in Biology and Medicine training program. Sam is the third Senes lab graduate student in the lab to be selected for the training grant, after Ben Mueller and Sam Condon. Her project focuses on high-throughput computational and experimental analysis of the GASright motif.

January 10, 2017
New publication: Ptc7p dephosphorylates select mitochondrial proteins to enhance metabolic function

Congratulations to Samson Condon for the publication of his latest paper in Cell Reports! Sam collaborated with Pagliarini and Coon groups and helped modeling the mechamism by which phosphorilatin regulates the activity of the mitochondrial phosphatase Prc7p.

  • Guo X, Niemi NM, Hutchins PD, Condon SGF, Jochem A, Ulbrich A, Higbee AJ, Russell JD, Senes A, Coon JJ, and Pagliarini DJ. "Ptc7p dephosphorylates select mitochondrial proteins to enhance metabolic function" Cell Reports 2017 18, 307-13 [PDF]
July 19, 2016
New publication: A high-throughput variant of the TOXCAT assay

Congratulations to Claire Armstrong for the publication of her first paper in Biochim. Biophys. Acta! She developed an asay that can help us determine association strength faster and more consistently than TOXCAT.

  • Armstrong CR and Senes A "Screening for transmembrane association in divisome proteins using TOXGREEN, a high-throughput variant of the TOXCAT assay Biochim. Biophys. Acta 2016 1858, 2573-83 [PDF]
April 20, 2016
New publication: Review article on computational design of membrane proteins

Alessandro publishes a review article in Nature Structural and Molecular Biology on the progress of the field of membrane protein design, in collaboration with his friend Patrick Barth (Baylor College of Medicine).

  • Barth P, Senes A "Toward high-resolution computational design of the structure and function of helical membrane proteins" Nat Struct Mol Biol 2016 23, 475-80 [PDF]
April 7, 2016
Congratulations fellowship recepients!

Congratulations to several fellowship recepients in the lab: graduate student Sam Anderson for being awarded the Dr. James Chieh-Hsia Mao Wisconsin Distinguished Graduate Fellowship for the 2016-17 academic year; graduate student Deena Mahbuba for being awarded the Steenbock Predoctoral Fellowship for the 2016-17 academic year; and undergraduate student Lucy Jiang for having been awarded a Biochemistry Undergraduate Summer Research Scholarship.

February 12, 2016
Good luck, Rika!

After sticking around for one more year as a postdoc in the lab, former graduate student Rika Khadria is moving to the University of North Carolina at Chapel Hill to be a postdoc in the lab of Mike Ramsey.

February 1, 2016
New postdoc Elizabeth Caselle joins the lab

The Senes lab welcomes Beth, who just received a PhD in Chemistry from joined from Syracuse University, where she worked in the Korendovych lab.

December 23, 2015
New publication: BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes

Congratulations to Sabareesh Subramaniam and Samson Condon for the publication of their latest paper in EMBO J! They collaborated with the Lin lab at the University of Oklahoma to predict how conformational changes mediate pore assembly for the apoptotic regulator Bax.

  • Zhang Z, Subramaniam S, Kale J, Liao C, Huang B, Brahmbhatt H, Condon SGF, Lapolla SM, Hays, FA, Ding J, He F, Zhang XC, Li J, Senes A, Andrews DW, Lin J. "BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes EMBO J 2016 35, 208-36 [PDF]
May 13, 2015
New publication: Review article on FRET for transmembrane helices

Congratulations to Rika Khadria for the publication of her latest review in Biopolymers! She discusses the various factors that contribute to performing effective FRET with transmembrane helices.

  • Khadria AS and Senes A "Fluorophores, environments and quantification techniques in the analysis of transmembrane helix interaction using FRET" Biopolymers 2015 104, 247-264 [PDF]
May 11, 2015
Dr. Ben!

Congratulations to Ben Mueller for successfully defending his PhD thesis in Biochemistry.

During his thesis, Ben has been studying an important transmembrane interaction motif using computational and experimental methods. He has also designed an algorithm that can predict transmembrane dimers from sequence alone. He has published three articles, with two more currently in preparation for submission.

Ben will move to the lab of Jens Meiler at Vanderbilt University at the end of the summer.

April 23, 2015
Congratulations fellowship recepients!

Congratulations to several fellowship recepients in the lab: graduate student Sam Craven for being awarded the Willaim H. Peterson Fellowship for the 2015-16 academic year; undergraduate student Evan Lange for having received a 2015-16 Wisconsin Hilldale Undegraduate/Facutly Reserach Fellowship; and undergraduate student Praisten Tiano for having been awarded a Biochemistry Undergraduate Summer Research Scholarship.

December 15, 2014
Three new PhD students join the lab!

The Senes lab welcomes Gladys Díaz-Vázquez (Biophysics program) and Sam Anderson and Deena Mahbuba (Biochemistry) who just joined!

December 1, 2014
Dr. Loren!

Congratulations to Loren LaPointe for successfully defending her PhD thesis in Biochemistry.

During her time in the lab, Loren has studied the structural organization of the complex formed by two essential proteins of the bacterial divisome, FtsB and FtsL. She has already published 3 papers, and more are likely to come. She will soon move to Tennessee to continue to work on membrane proteins, as a postdoc in the structural biology lab of Chuck Sanders at Vanderbilt University.

November 24, 2014
Dr. Rika!

Congratulations to Rika Khadria for successfully defending her PhD thesis in Biochemistry.

During her time in the lab, Rika has used FRET as a tool for understanding the association of membrane protein complexes. She has already published 4 papers, 3 of which are first author. Rika will stay in the lab for another year to continue single-molecule studies of the FtsB-FtsL complex in collaboration with Aaron Hoskins.

September 15, 2014
New publication: CATM prediction and experimental validation of a mitochondrial TM domain

Congratulations to Rika Khadria and Ben Mueller for the publication of their latest paper in JACS! In collaboration with Jon Stefely and Dave Pagliarini, they determined that the TM domain of the mitochondrial kinase ADCK3 self-associates, forming a GASright motif using an extended Gly-rich interface.

  • Khadria AS, Mueller BK, Stefely JA, Tan CH, Pagliarini DJ and Senes A "A Gly-zipper motif mediates homo-dimerization of the transmembrane domain of the mitochondrial kinase ADCK3" J Am Chem Soc 2014 136, 14068-77 [PDF]
September 3, 2014
New publication: A new backbone-dependent energy library

Congratulations to Sabareesh Subramaniam for the publication of his latest paper, an improved version of his previous energy-based conformer library for side chain modeling.

  • Subramaniam S and Senes A and "Backbone dependency further improves side chain prediction efficiency in the Energy-Based Conformer Library (bEBL)" Proteins 2014 81 (11), 3177-3187 [PDF]
July 1, 2014
Alessandro is promoted to Associate Professor

A major milestone for the lab was reached today, as Alessandro was promoted to Associate Professor with tenure!

March 13, 2014
Sam Condon is awarded a CIBM Predoctoral Traineeship

Sam is awarded a tranineeship with the Computation and Informatics in Biology and Medicine program. His project focuses on the computational and experimental analysis of desease causing mutation in membrane proteins from large scale data sets.

February 19, 2014
Dr. Sab!

Congratulations to Sabareesh Subramaniam for successfully defending his PhD thesis in Computational Biology.

During his time in the lab, Sab has published 5 papers, 3 of which are first author. Another first-author paper is currently under review and more are likely to come. Sab now works at VMware in Silicon Valley.

January 28, 2014
New publication: The fold of the Glycophorin A transmembrane dimer is optimized for formation of Cα-H hydrogen bonds

Congratulations to Ben Mueller and Sabareesh Subramaniam for the publication of their latest paper in PNAS! They demonstrated that a common motif for helix-helix interaction in membrane proteins is optimized for the formation of hydrogen bonds in which the donor is a carbon.

  • Mueller BK*, Subramaniam S* and Senes A "A frequent, GxxxG-mediated, transmembrane association motif is optimized for the formation of interhelical Cα-H hydrogen bonds" Proc Natl Acad Sci USA 2014 111(10) E888-95 (*authors contributed equally) [PDF]
November 21, 2013
Rika wins Science Magazine "Dance your PhD" prize

Congratulations to Rika Khadria for winning the first prize in Chemistry at the Dance your PhD competition, with an interpretative dance of her thesis project.

Find her video here.

Alessandro Senes
Associate Professor
Department of Biochemistry - UW-Madison
433 Backcock Dr., Room 419
Madison, WI 53706
office (+1) 608-890-2584
lab. (+1) 608-262-7355