The problem: Signaling across cell membranes
Many signals between cells are mediated by receptors in the membrane that sense extracellular events, like the release of neurotransmitters by a neighboring cell, the presence of hormones, or environmental cues like odors or antigens. The receptors transmit the signals across the membrane and initiate intracellular cascades. Our goal is to understand the interactions between receptors, how larger complexes are formed, and their dynamic behavior during signal processing.

The approach: Single molecule imaging
We use single molecule imaging to decipher molecular signaling events in living cells. With highly sensitive equipment, single fluorescently labeled receptors can be resolved. We label the proteins with the green fluorescent protein GFP, fluorescent proteins of other color, or with organic dyes. Single molecule experiments are able to give information that is complementary to bulk approaches because of the lack of ensemble averaging.

The technique: Total internal reflection fluorescence (TIRF) microscopy
A laser beam reaches the coverslip under such a steep angle that it is reflected back into the objective, and cannot penetrate into the sample space. However, parts of the sample that are very close to the coverslip, like the membrane of an attached cell, still can get illuminated. TIRF microscopy therefore allows to restrict the observation to the cell membrane and strongly reduce background from the inside of the cell. We can see single fluorescent molecules that reside in the membrane as bright spots against a dark background.

Please see also: http://www.ulbrich-lab.com/research.html

5 Selected Publications

Kleine Borgmann LAK., Ries J., Ewers H., Ulbrich MH.*, Graumann PL*. (2013) The bacterial SMC complex displays a novel mode of interaction with the chromosome. Cell Rep., 3: 1483-1492.

Hastie P.*, Ulbrich MH.*, Wang H., Arant RJ., Lau AG., Zhang Z., Isacoff EY., Chen L. (2013) AMPA receptor/TARP stoichiometry visualized by single molecule subunit counting. Proc Natl Acad Sci U S A., 110: 5163-5168.

Yu Y., Ulbrich MH., Li MH., Dobbins S., Zhang WK., Tong L., Isacoff EY., Yang J. (2012) Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex. Nat Commun., 3: 1252.

Ulbrich MH., Isacoff EY. (2008) Rules of engagement for NMDA receptor subunits. Proc Natl Acad Sci U S A., 105: 14163-14168.

Tombola F., Ulbrich MH., Isacoff EY. (2008) The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor. Neuron, 58: 546-556.

Fellowships, Awards and Honours

2009            NIH Pathway to Independence Award (K99/R00)
2006            Postdoctoral Fellowship of the American Heart Association (until 2008)
2004            Postdoctoral Fellowship of the German Research Association (until 2005)

• TIRF microscopy