Felix Lam

Postdoc

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Felix was born and raised in New York City where studied the violin, watched every episode of Star Trek and Star Trek: TNG, attended Hunter College and Stuyvesant High Schools, and was introduced to bench science in the lab of Seth Orlow at the NYU Medical Center. As an undergraduate at MIT, he continued research in the labs of Robert Weinberg and L. Mahadevan while rowing (proudly) as the lightest member of the men’s lightweight varsity crew team. After graduating, Felix joined the lab of George Church at the Harvard Medical School where, as a technician, he worked on developing cost-effective printed DNA microarray technology. Afterwards, as a graduate student with Erin O’Shea at UCSF, he studied promoter chromatin architecture and illuminated the rules by which nucleosomes modularize transcription tolerances and strengths. Northern California was also where Felix developed an interest in long distance running and where he completed the San Francisco Marathon 3 days before moving back to MIT for postdoctoral work. At present, he is enjoying all the physical inactivity and new father experiences that accompany the first born child.

Cellular toxicity from substrates and/or products in the fermentation medium remains one of the most complex and essential physiological constraints limiting higher production. We are taking both rational and inverse approaches to enhancing such a genetically intricate phenotype in yeast Saccharomyces cerevisiae. Thus far, we have uncovered a fundamental mechanism of general alcohol toxicity whereby alcohols impinge viability, not by solubilizing lipid bilayers, but by increasing plasma membrane permeability and dissipating the cell’s membrane potential. Since the yeast membrane is charged predominantly by opposing gradients of potassium (K+) and proton (H+) ions, elevating extracellular K+ and pH counteract these dissipating effects and significantly enhance tolerance and ethanol production. Currently, we are investigating the extent to which these approaches can apply to the feedstock toxicity present in lignocellulosic hydrolysates.

Email: flam (at) wi (dot) mit (dot) edu

 

Publications:

Shaw AJ, Lam FH, Hamilton M, Consiglio A, MacEwen K, Brevnova EE, Greenhagen E, LaTouf WG, South CR, van Dijken H, Stephanopoulos G. (2016) Metabolic engineering of microbial competitive advantage for industrial fermentation processes. Science. 353, 583–586.

Lam FH, Ghaderi A, Fink GR, Stephanopoulos G. (2014) Engineering alcohol tolerance in yeast. Science. 346, 71–75.

Lam FH, Hartner FS, Fink GR, Stephanopoulos G. (2010) Enhancing stress resistance and production phenotypes through transcriptome engineering. Methods in Enzymology: Guide to Yeast Genetics, 2nd Ed. 470, 509-532.

Lam FH, Steger DJ, O’Shea EK. (2008) Chromatin decouples promoter threshold from dynamic range. Nature. 453, 246-250.

Badarinarayana V, Estep PW, Shendure J, Edwards J, Tavazoie S, Lam FH, Church GM. (2001) Selection analyses of insertional mutants using subgenic-resolution arrays. Nature Biotech. 19, 1060-1065.