Adam C. Martin

Education

  • PhD, 2006, University of California, Berkeley
  • BS, 2000, Biology and Genetics, Cornell University

Research Summary

We study how cells and tissues change shape during embryonic development, giving rise to different body parts. We visualize these changes to determine how mechanical forces drive massive tissue movements in the fruit fly, Drosophila melanogaster. In addition, we also study the regulation of tissue integrity, investigating the processes that regulate the epithelial-to-mesenchymal transition or EMT.

Thomas U. Schwartz

Education

  • PhD, 2000, Free University of Berlin
  • MS, 1996, Biochemistry, Free University of Berlin
  • BS, 1993, Biochemistry, Free University of Berlin

Research Summary

Our primary goal is to understand how signals and molecules are transmitted between the nucleus and cytoplasm across the nuclear envelope. We work to decipher the mechanism and structure of the machinery that executes these cellular processes.

Rebecca Lamason

Education

  • PhD, 2011, The Johns Hopkins University School of Medicine
  • BS, 2002, Molecular Biology and Biotechnology, Millersville University

Research Summary

In the Lamason lab, we investigate how intracellular bacterial pathogens hijack host cell processes to promote infection. In particular, we study how Rickettsia parkeri and Listeria monocytogenes move through our tissues via a process called cell-to-cell spread. We utilize cellular, molecular, genetic, biochemical and biophysical approaches to elucidate the mechanisms of spread in order to reveal key aspects of pathogenesis and host cell biology.

Awards

  • NIH Pathway to Independence Award, 2015
Joseph (Joey) Davis

Education

  • PhD, 2010, MIT
  • BA,  2003, Computer Science, University of California, Berkeley
  • BS, 2003, Biological Engineering, University of California, Berkeley

Research Summary

The Davis lab is working to uncover how cells construct and degrade complex molecular machines rapidly and efficiently. We apply a variety of biochemical, biophysical, and structural approaches including quantitative mass spectrometry and single particle cryo-electron microscopy to understand the detailed molecular mechanisms of these processes. Ongoing projects in the lab are focused on autophagy, an essential eukaryotic protein and organelle degradation pathway, and assembly of the ribosome, which is essential in all cells.

Awards

  • Sloan Research Fellowship, Alfred P. Sloan Foundation, 2021
  • National Institute on Aging R00 Fellowship, 2017
  • National Institute on Aging K99 Fellowship, 2015
Stephen Bell

Education 

  • PhD, 1990, University of California, Berkeley
  • BS, 1985, Integrated Science Program and Biochemistry, Molecular Biology and Cell Biology, Northwestern University

Research Summary

We focus on the events that occur at the starting points of chromosome duplication. These DNA sequences — called “origins of replication” — are found at multiple sites on each eukaryotic chromosome and direct the assembly of replisomes, which replicate the DNA on both sides of the origin. We study this assembly process to understand how chromosomes are replicated, and how these events are regulated during the cell cycle to ensure genome maintenance.

Awards

  • National Academy of Sciences, Member, 2017
  • National Academy of Sciences Award in Molecular Biology, 2009
  • Howard Hughes Medical Institute, HHMI Investigator, 2000
Revealing an imperfect actor in plant biotechnology

Whitehead Institute researchers detect the chemical mistakes of a common herbicide-resistance enzyme, then successfully re-engineer it for enhanced precision.

Nicole Davis | Whitehead Institute
November 29, 2017

A research team led by MIT’s Whitehead Institute for Biomedical Research has harnessed metabolomic technologies to unravel the molecular activities of a key protein that enables plants to withstand a common herbicide.

Their findings reveal how the protein — a kind of catalyst or enzyme first isolated in bacteria and introduced into plants such as corn and soybeans in the 1990s — can sometimes act imprecisely, and how it can be successfully re-engineered to be more precise. The new study, which appears online in the journal Nature Plants, raises the standards for bioengineering in the 21st century.

“Our work underscores a critical aspect of bioengineering that we are now becoming technically able to address,” says senior author Jing-Ke Weng, a member of the Whitehead Institute and an assistant professor of biology at MIT. “We know that enzymes can behave indiscriminately. Now, we have the scientific capabilities to detect their molecular side effects, and we can leverage those insights to design smarter enzymes with enhanced specificity.”

Plants provide an extraordinary model for scientists to study how metabolism changes over time. Because they cannot escape from predators or search for new food sources when supplies run low, plants must often grapple with an array of environmental insults using what is readily available — their own internal biochemistry.

“Although they appear to be stationary, plants have rapidly evolving metabolic systems,” Weng explains. “Now, we can gain an unprecedented view of these changes because of cutting-edge techniques like metabolomics, allowing us to analyze metabolites and other biochemicals on a broad scale.”

Key players in this evolutionary process, and a major focus of research in Weng’s laboratory, are enzymes. Traditionally, these naturally occurring catalysts have been viewed as mini-machines, taking the proper starting material (or substrate) and flawlessly converting it to the correct product. But Weng and other scientists now recognize that they make mistakes, often by latching on to an unintended substrate.

“This concept, known as enzyme promiscuity, has a variety of implications, both in enzyme evolution and more broadly, in human disease,” Weng says.

It also has implications for bioengineering, as Bastien Christ, a postdoctoral fellow in Weng’s laboratory, and his colleagues recently discovered.

Christ, then a graduate student in Stefan Hörtensteiner’s lab at the University of Zurich in Switzerland, was studying a particular strain of the flowering plant Arabidopsis thaliana as part of a separate project when he made a puzzling observation. He found that two biochemical compounds were present at unusually high levels in the plant’s leaves.

Strangely, these compounds (called acetyl-aminoadipate and acetyl-tryptophan) weren’t present in any of the normal, so-called wild type plants. As he and his colleagues searched for an explanation, they narrowed in on the source: an enzyme, called BAR, that was engineered into the plants as a kind of chemical beacon, enabling scientists to more readily study them.

But BAR is more than just a tool for scientists. It is also one of the most commonly deployed traits in genetically modified crops such as soybeans, corn, and cotton, enabling them to withstand a widely-used herbicide (known as phosphinothricin or glufosinate).

For decades, scientists have known that BAR, originally isolated from bacteria, can render the herbicide inactive by tacking on a short string of chemicals, made of two carbons and one oxygen (also called an acetyl group). As the researchers describe in their Nature Plants paper, BAR has a promiscuous side, and can work on other substrates, too, such as the amino acids tryptophan and aminoadipate (a lysine derivative).

That explains why they can detect the unintended products (acetyl-tryptophan and acetyl-aminoadipate) in crops genetically engineered to carry BAR, such as soybeans and canola.

Their research included detailed studies of the BAR protein, including crystal structures of the protein bound to its substrates. This provided them with a blueprint for how to strategically modify BAR to make it less promiscuous, and favor only the herbicide as a substrate and not the amino acids. Christ and his colleagues created several versions that lack the non-specific activity of the original BAR protein.

“These are natural catalysts, so when we borrow them from an organism and put them into another, they may not necessarily be perfect for our purposes,” Christ says. “Gathering this kind of fundamental knowledge about how enzymes work and how their structure influences function can teach us how to select the best tools for bioengineering.”

There are other important lessons, too. When the BAR trait was first evaluated by the U.S. Food and Drug Administration (FDA) in 1995 for use in canola, and in subsequent years for other crops, metabolomics was largely non-existent as a technology for biomedical research. Therefore, it could not be applied toward the characterization of genetically engineered plants and foods, as part of their regulatory review. Nevertheless, acetyl-aminoadipate and acetyl-tryptophan, which are normally present in humans, have been reviewed by the FDA and are safe for human and animal consumption.

Weng and his colleagues believe their study makes a strong case for considering metabolomics analyses as part of the review process for future genetically engineered crops.

“This is a cautionary tale,” Weng says.

The work was supported by the Swiss National Science Foundation, the EU-funded Plant Fellows program, the Pew Scholar Program in the Biomedical Sciences, and the Searle Scholars Program.

Muscle plays surprising role in tissue regeneration

Whitehead Institute researchers have pinpointed distinct muscle subsets that orchestrate and pattern regrowth.

Nicole Davis | Whitehead Institute
November 22, 2017

Researchers at the Whitehead Institute have illuminated an important role for different subtypes of muscle cells in orchestrating the process of tissue regeneration.

In a paper appearing online today in Nature, they reveal that a subtype of muscle fibers in flatworms is required for triggering the activity of genes that initiate the regeneration program. Notably, in the absence of these muscles, regeneration fails to proceed. Another type of muscle, they report, is required for giving regenerated tissue the proper pattern — for example, forming one head instead of two.

“One of the central mysteries in organ and tissue regeneration is: How do animals initiate all of the cellular and molecular steps that lead to regeneration?” says senior author Peter Reddien, a member of Whitehead Institute, professor of biology at MIT, and investigator with the Howard Hughes Medical Institute. “We’ve helped answer this question by revealing a surprising molecular program that operates within a subgroup of muscle cells that helps establish the molecular information required for proper tissue regeneration after injury.”

For more than a decade, Reddien and the researchers in his laboratory have studied the biological mechanisms that underlie regeneration in a tiny flatworm called planarians. These worms possess some impressive regenerative capabilities: When sliced in two, each piece of the worm can regrow the body parts needed to form two complete organisms. In previous studies, Reddien’s team identified a set of always-on genes, known as position control genes (PCGs), that provide cells with region-specific instructions, like a set of GPS coordinates, that tell cells where they are in the body, and thus what body part to regenerate. Interestingly, PGCs are active in planarian muscle cells, suggesting muscle may play a major role in the regeneration process.

“This discovery raised a lot of questions about how muscle participates in this process,” Reddien says.

In planarians, there are a handful of muscle cell types. For example, if you imagine the worms as simple cylindrical tubes, there are longitudinal muscle fibers, which run head-to-tail along the tubes’ long axis. There are also circular fibers, which are perpendicular to the longitudinal fibers and hug the tubes’ outer circumference.

To assess the roles of these different muscle cell types in regeneration, first author Lucila Scimone and her colleagues needed a method to selectively remove them. When myoD, a gene found specifically in the longitudinal fibers, is inhibited, those fibers fail to form. Similarly, the nkx1-1 gene marks the circular fibers, and when its function is reduced, they do not develop. Using these genes as molecular scalpels, Scimone and her co-authors could test the effects of ablating these distinct muscle groups on regeneration.

Surprisingly, when the longitudinal fibers were removed, the results were dramatic. The worms live quite normally, but when they are injured (the head removed, for example) they cannot regenerate the missing parts.

“This is an amazing result; it tells us that these longitudinal fibers are essential for orchestrating the regeneration program from the very beginning,” says Scimone, a scientist in Reddien’s lab.

As the researchers dug deeper into the finding, they learned that the functions of two critical genes are disrupted when longitudinal fibers are missing. These genes, called notum and follistatin, are known for their fundamental roles in regeneration, controlling head-versus-tail decisions and sustained cell proliferation, respectively, following tissue injury.

In addition to this essential role for longitudinal fibers, the research team also uncovered a key role for circular fibers. When these muscles are missing, planarians are able to regenerate missing body parts, but what regrows is abnormally patterned. For example, two heads may be regenerated within a single outgrowth, instead of one.

These results underscore an important and previously unappreciated role for muscle, widely known for its contractile properties, in instructing the tissue regeneration program. The Whitehead researchers will continue to probe the role of different muscle cell types in planarian regeneration and also explore whether other animals with regenerative capabilities possess a similar muscle-localized program for conferring positional information.

“It’s hard to understand what limits humans’ abilities to regenerate and repair wounds without first knowing what mechanisms are enabling some animals, like planarians, to do it so amazingly well,” Reddien says.

This work was supported by the National Institutes of Health, Howard Hughes Medical Institute, and the Eleanor Schwartz Charitable Foundation.

Elly Nedivi

Education

  • PhD, 1991, Stanford University
  • BSc, 1982, Biology and Biochemistry, Hebrew University, Israel

Research Summary

The property of the brain that allows it to constantly adapt to change is termed plasticity, and is a prominent feature not only of learning and memory in the adult, but also of brain development. Connections between neurons (synapses) that are frequently used become stronger, while those that are unstimulated gradually dwindle away. The Nedivi lab works to identify the cellular mechanisms that underlie the addition and elimination of synaptic connections in response to activity using genetic and in vivo imaging approaches.

Awards

  • Elected Member at Large, AAAS, 2019-2023
  • Elected Member, Dana Alliance, 2019
  • BCS Award for Excellence in Undergraduate Teaching, 2018
  • American Association for the Advancement of Science (AAAS), Fellow, 2016
  • AFAR Julie Martin Mid-Career Award in Aging Research, 2007 – 2011
  • Edgerly Innovation Fund Award, 2006
  • Dean’s Education and Student Advising Award, 2003
  • NSF Powre Award, 1999
  • Alfred P . Sloan Research Fellowship, 1999 – 2001
  • Ellison Medical Foundation New Scholar Award, 1997 – 2002
Phillip A. Sharp

Education

  • PhD, 1969, University of Illinois, Urbana-Champaign
  • BA, 1966, Chemistry and Math, Union College

Research Summary

We investigate small, non-coding RNAs called microRNAs (miRNAs), which regulate over half of the genes in mammalian cells at the stages of translation and mRNA stability. We are also interested in the processes underlying transcription from the anti-sense strand (so-called “divergent” transcription), as well as the relationship between elongation of transcription, RNA splicing, and chromatin modifications.

Awards

  • AACR Award for Lifetime Achievement in Cancer Research, 2020
  • AACR Distinguished Award for Extraordinary Scientific Innovation and Exceptional Leadership in Cancer Research and Biomedical Science, 2018
  • Royal Society of London, Foreign Fellow, 2011
  • National Science Foundation, National Medal of Science, 2004
  • The Nobel Foundation, Nobel Prize in Physiology or Medicine, 1993
  • National Academy of Medicine, Member, 1991
  • American Association for the Advancement of Science, Fellow, 1987
  • American Academy of Arts and Sciences, Fellow, 1987
  • National Academy of Sciences, Member, 1983
Harvey F. Lodish

Education

  • PhD, 1966, Rockefeller University
  • BS, 1962, Chemistry and Mathematics, Kenyon College

Research Summary

Harvey Lodish has been a leader in molecular cell biology as well as a biotechnology entrepreneur for over five decades. Much of his early research focused on the regulation of messenger RNA translation and the biogenesis of plasma membrane glycoproteins. Beginning in the 1980s, his research focused on cloning and characterizing many proteins, microRNAs, and long noncoding RNAs important for red cell development and function. His laboratory was the first to clone and sequence mRNAs encoding many hormone receptors, mammalian glucose transport proteins, and proteins important for adipose cell formation and function. He went on to identify and characterize several genes and proteins involved in insulin resistance and stress responses in adipose cells. Over the years, he has mentored hundreds of undergraduates, PhD and MD/PhD students, and postdoctoral fellows, and continues to teach award-winning undergraduate and graduate classes on biotechnology.

Harvey Lodish closed his lab in 2020 and is no longer accepting students.

Awards

  • Wallace H. Coulter Award for Lifetime Achievement in Hematology, American Society of Hematology, 2021
  • Donald Metcalf Award, International Society for Experimental Hematology, 2020
  • American Society for Cell Biology WICB Sandra K. Masur Senior Leadership Award, 2017
  • Pioneer Award, Diamond Blackfan Anemia Foundation, 2016
  • Mentor Award in Basic Science, American Society of Hematology, 2010
  • President, American Society for Cell Biology, 2004
  • Associate Member, European Molecular Biology Organization (EMBO), 1996
  • National Academy of Sciences, Member, 1987
  • American Academy of Arts and Sciences, Fellow, 1986
  • John Simon Guggenheim Memorial Foundation, Guggenheim Fellowship, 1977