• 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 G protein signaling. He has been investigating PTMs since 2001. He is also a co-director of the Systems Mass Spectrometry Core (SYMS-C) facility at Georgia Tech.

    Wei Li, PhD

    Postdoctoral Fellow

    Wei is working on proteomics of the extra-cellular matrix and also on developing methods for identifying phosphorylation-mediated protein transitions from states of disorder to order. 

    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.

    Xinya Su

    PhD Graduate Student - Biological Sciences

    Xinya is conducting kinome-wide screens to identify kinases involved in the regulation of G protein gamma subunits and G protein signaling.

    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!

    Jiani Long, MS

    MS Graduate in Bioinformatics

    Jiani made amazing strides in domain family SAPH-ire analysis for our lab, which we are incorporating into the traditional familial analysis workflow now. She is currently in Boston working as a bioinformatics consultant. 

    Ragy Haddad, MS

    MS Graduate in Bioinformatics

    Ragy is the first to develop a user friendly and web-accessible tool for SAPH-ire, which we will release very soon! He is now a computational biologist at DeepBiome at Harvard Life Labs.

    Kuntal Mukherjee, PhD

    Research Scientist II

    Kuntal used yeast to test the function of phosphorylation hotspots predicted by SAPH-ire. He discovered that phosphorylation of linker histones plays a very important role in DNA maintenance. He is now studying the incorporation of RNA into DNA in Francesca Storici's lab.

  • Highlighted Publications

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

    For a complete list of publications click here.

    Citrullination of fibronectin alters integrin clustering and focal adhesion stability promoting stromal cell invasion.

    Stefanelli, Choudhury, Hu, Liu, Schwenzer, Yeh, Chambers, Pesson, Li W, Segura, Midwood, Torres, Barker*; Matrix Biology (2019)

    Here we used mass spectrometry to discover citrullination sites on fibronectin, the role of this PTM on cell motility and in the immune response of patients with rheumatoid arthritis.

    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.

    Quantitative BioSciences Student Appreciation Lunch

    Appreciating all that Nolan does for our lab....and eating pizza!

    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.

  • Outreach Content - Middle School

    Here are a few useful links and images for outreach in protein biochemistry!

    Protein Gel Electrophoresis Time-Lapse

    This is what our protein gels would look like if you could speed up time!

    Enzymes!

    This is an outstanding video from Sheila Marsh at Stanford University

    Amylase - An Enzyme that Breaks Down Starch!

    Here is an experiment that shows the ability of amylase to breakdown starch in a test tube!

    This is the enzyme alpha-Amylase, which is found in your saliva!

    The blue are amino acids in the enzyme. The yellow is starch bound at the active site of the enzyme.

    Zooming into the enzyme Amylase!

    This is one long chain of amino acids! The active site is where the yellow starch molecules are seen here. The white and red balls and sticks on the right correspond to amino acid side chains that help to catalyze the breakdown of the starch.

    What is the most powerful enzyme we know of?

    OMP Decarboxylase is VERY good at doing a tough job.

    Molecular Evolution - All Life on Earth Shares a Common Ancestor!

    We share the same code!

    Do Proteins Evolve? - Molecular Evolution

    Sequences of myoglobin from five different animals are compared to create a phylogenetic tree. Each molecule is colored to show differences from the human protein. Amino acids that are identical are pink, amino acids that are different but similar are lighter pink, and amino acids that are completely different are in white. The heme is shown in bright red. The tree was calculated with the online server at phylogeny.fr. PDB entries 3rgk, 1ymb, 1mbo, 1lhs, 2nrl. Re-posted from our brilliant friends at the PDB! https://pdb101.rcsb.org/motm/206

    Amylase from Henderson Middle Students!

    We visit Ms. Shaw's and Ms. Clarke's science classes and asked for volunteer students to provide saliva samples that we could analyze by gel electrophoresis. We were able to detect the enzyme Amylase in each student's saliva sample! Some other bigger and smaller proteins were also visible. We compared this to a protein sample from a cell (where we expected to see thousands of proteins)....and we see many more bands.

  • Outreach Content - Elementary School

    Here are a few useful links and images for outreach at the Elementary School level

    The Scientific Method

    Here is a great video for young students to help them learn the scientific method.

    The Scientific Method is Simple!

    • It all starts with paying close attention to the world around you (making careful observations)
    • When you identify something that is interesting to you....you ask questions about it to learn more!
    • Once you learn something by looking around, you can make a hypothesis (a prediction) that is testable.
    • Now, you test your prediction using experimentation! We always have controls and variables and we try to test one variable at a time.
    • Once we have our experimental results (the data!), we analyze them to see if our prediction was correct or not.
    • Finally we make a conclusion!....We conclude that our prediction was right or wrong.
    • MOST IMPORTANTLY!.....we do not get upset when our predictions are wrong (i.e. not confirmed by the experimental results)! No no no...it simply means we have to try again by making a new prediction. Eventually, we will find the answer. 
    • This is how research works and is useful for discovery of new planets to curing bad diseases like cancer!

    First Grader Scientists at Ridgepoint Elementary School!

    I visit Mrs. Torres' first grade elementary school class at Ridgepoint Elementary School in Sacramento California to teach them the scientific method. The kids were AWESOME!!!!

     

    We started by OBSERVING each others arms (students only).

     

    Next - we asked the QUESTION: "Which student has the longest wingspan?"

     

    Then we all sat down and formulated a HYPOTHESIS, where each student PREDICTED who they thought had the longest arms/wingspan.

     

    Then we did an EXPERIMENT where we measured everyone's wingspan to test our individual hypotheses.

     

    We ANALYZED THE DATA (pictured above) by putting all of the results into a bar graph.

     

    Lastly, we drew a CONCLUSION about who had the longest wingspan based on the data. Students could then see if their hypothesis was supported by the data or not!

    A First Grader's Thank You...

    Mrs. Torres' class was such a pleasure! They even sent me thank you notes, some of which I show here. Thank you little scientists!

  • Contact Us!

    Matthew Torres, PhD

    School of Biological Sciences

    Georgia Institute of Technology

    Engineered Biosystems Building (EBB) - Office 4009

    950 Atlantic Drive

    Atlanta GA, 30332

    mtorres35@gatech.edu

    404-385-0401 (Office)