• A CHALLENGE OF OUR TIME

    Post-translational modifications (PTMs): Chemical or proteinaceous modifications that occur on proteins after their translation inside living cells, and essential for several life processes including cell division, signaling, epigenetic regulation, and more.

    An Exponential Problem

    Since the discovery of protein phosphorylation in the early 1950s, our ability to detect PTMs has increased exponentially. Over 300 different types of PTM are now known to exist - phosphorylation being the most common. We know now that most (if not all) proteins become modified and regulated at some point during the life of a cell. This rapid expansion of knowledge presents a challenge for the biologists of our time who seek to understand how cells work.

    Our "State" of Knowledge

    In 2017, well over 600,000 experimentally verified unique PTMs have been publicly curated (equivalent to the combined area of the red states). In comparison, only ~10,000 (~2%) have been experimentally verified as biologically functional (equivalent to the size of Vermont)!

    Thus, the rate at which we can experimentally detect PTMs now far surpasses the rate at which we can understand their biological significance through purely empirical means.

    Fundamental Implications

    We believe that finding solutions to these challenges will fundamentally impact our understanding of cell biology and provide new avenues and opportunities for improving and protecting human health.

  • OUR MISSION

    Our goal is to understand how PTMs regulate protein structure, function, and cell behavior.

     

    We approach this challenge using three primary tools:

    The yeast eukaryotic cell model

    Mass Spectrometry

    Bioinformatics

     

    We address questions at multiple levels of complexity - from proteome to protein.

  • What We Do

    Our research spans three major areas of focus

    Systematic Analysis of PTM Hotspots (SAPH-ire)

    A computational solution

    We develop computational tools for the prediction of PTM function potential. SAPH-ire is our premier tool, which utilizes machine learning to prioritize PTMs for experimental analysis. We are also using SAPH-ire to explore other types of protein features.

    PTMs as Regulators of

    G Protein Signaling

    From computation to experimentation

    We study how PTMs regulate G protein signaling - a process responsible for the transduction of hormones, neurotransmitters, and even photons of light. G protein signaling systems are the most prominent targets for the pharmaceutical treatment of disease.

    Mass Spectrometry & Proteomics

    Deciphering PTM codes

    We utilize mass spectrometry to study PTMs on proteins extracted from cells. We also collaborate with mechanical engineers who are helping us to improve the sensitivity of mass spectrometers for the analysis of combinatorial PTM on individual proteins.

  • The Team

    We are always seeking extraordinary new members to contribute. Here is our current group.

    Matt Torres, PhD

    Principal Investigator

    Matt is a former Tar Heel from UNC Chapel Hill. His training is in mass spectrometry-based proteomics and he has been investigating PTMs since 2001. He is also the co-director of the Systems Mass Spectrometry Core (SYMS-C) facility at Georgia Tech.

    Kuntal Mukherjee, PhD

    Research Scientist II

    Kuntal is using yeast and human model systems to evaluate PTM hotspots predicted by SAPH-ire. He is also a mentor for several of the students in the wet lab.

    Alex Jonke, PhD

    Research Scientist II

    Alex is a GT-trained analytical chemist contributing to several proteomics projects including the development of a novel ion source for improved MS detection of proteins (in collaboration with the Fedorov Lab at GT).

    Maneesha Aluru, PhD

    Visiting Research Assist. Prof.

    Maneesha has been leading the systems biology branch of the lab and is studying molecular mechanisms of aging linked to G protein and other MAPK signaling pathways.

    Zahra Nassiri-Toosi

    PhD Candidate - Biological Sciences

    Zahra is exploring the phosphorylation dynamics of G proteins in response to cellular stress.

    Hyojung Kim

    PhD Candidate - Chemistry and Biochemistry

    Hyojung is studying proteome dynamics in response to cellular stress and heme homeostasis.

    Nolan English

    PhD Candidate - Quantitative Biosciences

    Nolan is establishing a new, state-of-the-art PTM database that he will combine with existing datasets to explore computational models for human disease.

    Jiani Long

    MS Graduate Student - Bioinformatics

    Jiani is working on feature extraction from protein sequence and structure, for use in SAPH-ire. She has made incredible strides in domain family PTM analysis using TensorFlow machine learning models.

    Ragy Haddad

    MS Graduate Student - Bioinformatics

    Ragy is developing a new user interface for SAPH-ire and a new PTM repository.

    Linglin Zhang

    MS Graduate Student - Bioinformatics

    Linglin is developing new methods to detect functional PTMs in eukaryotes.

  • Former Team Members

    These are folks that have come and gone. We thank them for the contributions they've made!

    Shilpa Choudhury, PhD

    Torres Lab Graduate - Biological Sciences

    Shilpa is credited with several discoveries in the lab centering on the phosphoregulation of G protein signaling. She is also our first PhD graduate and is now gifting her talents as a post-doctoral fellow at Genentech!

    Rushika Pandya, MS

    MS Graduate in Bioinformatics

    Rushika investigated the PTM topologies of RGS protein domain families and in curating data for a new PTM database. She was very successful, with 2 publications in 1.5 years and a third one on the way! She is now at the UCSF Bioinformatics core facility!

    Ramya Madupuri, MS

    MS Graduate in Bioinformatics

    Ramya is an incredible bioinformatician who significantly advanced our understanding of PTMs based on protein structural studies. She is now applying creative bioinformatics techniques to study cancer at Memorial Sloan Kettering Cancer Center!

    Niveda Sundararaman, MS

    MS Graduate in Bioinformatics

    Niveda was instrumental in establishing alternative uses for the SAPH-ire algorithm. She now is working at Cedar-Sinai Medical Center as a proteomics bioinformatician!

    Paris
    Baradaran-Mashinchi

    Undergraduate Researcher

    Paris was an undergraduate student who helped Shilpa to create yeast strains that harbor PTM site mutations. She's now in medical school training to heal people!

    Henry Dewhurst, MS

    MS Graduate in Bioinformatics

    Henry was instrumental in the early development stages of SAPH-ire.

    Tori McKinney, BS

    Lab Manager

    Tori started with us as an undergraduate and made significant contributions to studies in yeast aging under the mentorship of Maneesha Aluru. She later became our lab manager and kept us all in line!

    Nagender Panyala, PhD

    Post-Doctoral Fellow

    Nagender established preliminary studies in protein cross linking and top-down proteomics in our lab.

    Anne-Kathryn (A.K.) Love-Venerro, BS

    Lab Manager

    AK started as an undergraduate in our lab and quickly excelled to lab manager. She helped to create several yeast strains that we use to this day! She is now at the CDC saving us from who knows what!

    Krishna Vukoti, PhD

    Research Scientist II

    Krish was instrumental in helping the lab get off the ground. His focus was on using mass spectrometry to study proteolytic cleavage by membrane aspartyl proteases. You may know his son who is a world champion speller!

    Charlie Winter, BS

    Lab Manager

    Charlie was our first lab manager and did an amazing job helping to build the lab from nothing to something!

  • Publications

    Selected work from the Torres Lab at Georgia Tech (*corresponding author).

    For a complete list of publications click here.

    The dynamic and stress-adaptive signaling hub of 14-3-3: Emerging mechanisms of regulation and context-dependent protein-protein interactions

    Pennington, Chan, Torres, Anderson*; Oncogene (2018)

    This review covers a wide range of 14-3-3 regulatory mechanisms including PTM. We used SAPH-ire to thoroughly predict the function potential of experimental PTMs observed on 14-3-3 proteins across eukaryotes - only some of which have been studied previously. Among the more interesting discoveries was that the family harbors 4 distinct clusters of PTM - two of which were unrealized previously.

    Negative Feedback Phosphorylation
    of G gamma Subunit Ste18 and the Ste5 Scaffold Synergistically Regulates MAPK Activation in Yeast

    Choudhury, Baradaran-Mashinchi, Torres*; Cell Reports (2018)

    This work demonstrates for the first time that G gamma (Gg) subunits, besides acting as anchors for their obligate G beta (Gb) subunits, have more complex roles in regulating G protein signaling. Furthermore, they show that this tuning of G protein signaling by the phosphorylated Gg N-terminal tail is achieved by altering the interaction between Gbg and downstream effectors in a PTM-dependent manner.

    Mitogen-activated protein kinases, Fus3 and Kss1, regulate chronological lifespan in yeast.

    Aluru, McKinney, Venero, Choudhury, Torres*; Aging (2017)

    Dr. Maneesha Aluru and team discovered that specific MAPKs thought to have very restricted roles in the process of yeast mating are in fact important regulators of cellular longevity. 

    Predicted functional implications of phosphorylation of RGS proteins in plants

    Tunc-Ozdemir, Li, Jaiswal, Urano, Jones*, Torres*; Frontiers in Plant Science (2017)

    In this project, we utilized several elements of SAPH-ire to explore the relationships and functional implications of plant and mammalian PTMs found on Regulator of G protein Signaling (RGS) proteins.

    Acylation of SOD1 at K122 governs SOD1-mediated inhibition of mitochondrial respiration

    Banks,Rodriquez, Gashler, Pandya, Mortenson, Whited, Soderblom, Thompson, Moseley, Reddi, Tessem, Torres, Anderson*; Mol. Cell Biol. (2017)

    Using SAPH-ire, we identified PTMs with elevated function potential in superoxide dismutase proteins. One of these ranking in the top 10 (K122 acylation) was tested and found to have an important function in regulating mitochondrial respiration.

    Systematic analysis of PTM features for function potential prediction

    Dewhurst and Torres*; PLOS ONE (2017)

    Here we describe the impact of PTM features on function potential prediction by SAPH-ire.

    Proteome-wide structural analysis of PTM hotspots reveals regulatory elements predicted to impact biological function and disease

    Torres*, Dewhurst, Sundararaman; Molecular and Cellular Proteomics (2016)

    Here we demonstrate a neural network machine learning approach for prediction of functional PTMs.

    Heterotrimeric G protein ubiquitination as a regulator of G-protein signaling

    Torres*; in Progress in Molecular Biology and Translational Science (2016)

    A review of heterotrimeric G protein regulation by ubiquitination including a comparison of ubiquitin site topologies between large and small G proteins.

    Catalytic properties of intramembrane aspartyl protease substrate hydrolysis evaluated using a FRET peptide cleavage assay

    Naing, Vukoti, Drury, Johnson, Kalyoncu, Hill, Torres, Lieberman*; ACS Chemical Biology (2015)

    Here we characterized the proteolytic cleavage site preference of an intramembrane aspartyl protease by mass spectrometry.

    Structural Analysis of PTM Hotspots (SAPH-ire): A quantitative informatics method enabling the discovery of novel regulatory elements in protein families

    Dewhurst, Choudhury, Torres*; Molecular and Cellular Proteomics (2015)

    The inaugural proof-of-principle test for SAPH-ire, showing that integration of PTM features serves to improve prediction of functional PTMs. Using the approach, we discovered novel PTM regulatory elements in heterotrimeric G protein systems.

    Deciphering post-translational modification codes

    Lothrop, Torres*, Fuchs*; Febs Letters (2013)

    This manuscript highlights several examples of combinatorial PTMs in proteins, and describes recent technological developments, which are driving our ability to understand how PTM patterns may "code" for biological outcomes.

  • In The News....

    We thank those who have taken notice and decided to say something about it!

    Uncovering a Hidden Protein “Tail” that Puts the Brakes on Cell Signaling

    By John Toon (2018)

    Using an informatics tool that identifies “hotspots” of post-translational modification (PTM) activity on proteins, researchers have found a previously-unknown mechanism that puts the brakes on an important cell signaling process involving the G proteins found in most living organisms. (Click Here for More Info)

    SAPH-ire Helps Scientists Prioritize Protein Modification ResearchTitle Text

    By John Toon (2015)

    Researchers have developed a new informatics technology that analyzes existing data repositories of protein modifications and 3D protein structures to help scientists identify and target research on “hotspots” most likely to be important for biological function.

    (Click Here for More Info)

    SAPH-ire: Structural analysis of PTM hotspots!

    By Ben Orsburn (2015)

    Continuing theme alert! What do we do with all of this proteomics PTM data? Maybe we run it through this awesome new program from Henry Dewhurst et al., that they call SAPH-ire..... 

    (Click Here for More Info)

  • Some Fun Had By All

    ....and random things to celebrate.

    Masters Rushika and Rumya Graduate!!!

    Can't believe they are on their way! We are so happy to have worked with them and proud of their contributions to our science. CONGRATULATIONS!!!

    Graduation thumbs up from the PhD students and Postdocs!

    December 2017

    Painted Pin Bowling 2017!!

    ...minus a few folks who had to bowl and dash!

    A motley crew of bowlers! Painted Pin party 2017!!!

    This was a send off party for Tori on her last day at Tech! We'll miss you Tori!

    Painted Pin

    Tori (and Tim) stand onlooking and hesitant to approach the bowling lane! Sadegh (Zahra's husband) looks on with suspicion.

    Painted Pin

    Hyojung and Shilpa pause from their discussion about whether there is a penalty for throwing the bowling ball backwards....

    Painted Pin

    Paris was on fire this night. She had Zahra and Sadegh in stitches - or at least she was in stitches.

    Painted Pin

    Rushika and Ramya - shortly after throwing the bowling ball backwards....

    Painted Pin

    Torres and Tori head to head for the last time!

    Tie-Dye 2015!!

    The Torres lab and families got together for food, ping pong, and tie dye!!!

    Tie-Dye 2013!!

    The inaugural tie-dye event.

  • Contact Us!

    We Like to Find New Ways to Push the Science Forward!

     

    Our lab is located in the EBB1 building at Georgia Tech (see below).

    950 Atlantic Drive, 30332
    404-385-0401 (o)