Statement of Work: Dr. Peter Burbelo

1\. [Objectives]{.underline}

The contractor will work with Dr. Michael Iadarola and other members of
the Neurobiology and Pain Therapeutics Section. The contractor will
conduct multidisciplinary molecular, biochemical, pharmacological, and
clinical laboratory research. Dr. Peter Burbelo\'s work will focus on
understanding mechanisms of chronic pain, methods of treating chronic
pain, and mechanisms of other neurological diseases related to injury,
inflammation or infection using state-of-the-art biochemical and
molecular biological methodology. The contractor will work with Dr.
Michael Iadarola and other members of the Neurobiology and Pain
Therapeutics Section. The areas of investigation include examination of
vanilloid agonists such as resiniferatoxin and their effect on
inflammatory process in the periphery and their ability to induce
nervous system plasticity and gene regulation in specific neurons and
neural circuits and more broadly in the brain or other organs if
indicated. These studies will be conducted in cell lines, primary
cultures of nervous system cells as well as *in vivo* studies using
animal models. Dr. Burbelo will also be involved in analysis of human
clinical samples obtained from patients with various neurological
disorders. These studies are aimed primarily at patients with chronic
pain disorders but will include a variety of other conditions in which
an autoimmune process has been hypothesized or demonstrated such as
paraneoplastic syndromes, multiple sclerosis and infectious diseases,
especially viral diseases that affect sensory neurons.

2\. [Approach]{.underline}

The contractor will be involved in implementing state-of-the-art cell
biology and molecular biological methods for analysis of neural circuits
and induced gene expression during states of pharmacological,
physiological or pathophysiological activation and the treatment of such
states. The contractor will be involved in analysis human neurological
disorders and in animal models or in vitro cells that model such
disorders, especially those related to pain and nerve injury.

3\. [Methods]{.underline}

The services that will be performed are as follows:

a\) The contractor will participate in ongoing research in the
laboratory related to experimental pain control using both in vitro cell
lines and primary cultures, use of genetically encoded reporter systems
and expertise in construction of targeting vectors for transgenic and
gene deletion studies. These include studies related to vanilloid
agonists such as RTX and other compounds developed by the laboratory.

b\) The contractor must have a working knowledge of and experience in
signal transduction, gene regulation and molecular biology. The
contractor must have a strong background in generating mammalian and
bacterial expression vectors, mutagenesis, high-throughput cloning, cell
biology and immunofluorescence imaging of cells, and experience in
protein/DNA sequence analysis. The contractor must have a working
knowledge of and experience in disease diagnostics. Priority will be
given to candidates with expertise in generating humoral response
profiles to panels of recombinant eukaryotic antigens.

c\) The contractor will implement a new assay he has developed for
detection of serum antibodies based on liquid-phase antigen antibody
interaction, use of Renilla Luciferase-based fusion proteins as antigens
and expression of antigens in mammalian cell systems. This assay will be
adapted to our BioMek robotic pipeting platform and readings will be
made via a luminometer. The contractor will make measurements of serum
antibodies in various patient cohorts using this assay. The contractor
is expected to be capable of independently conducting all phases of the
assay, assessment of the resulting data and modification and refinements
of the methodology as needed.

d\) The contractor will maintain detailed records of experimental
procedures and results. High quality laboratory notebooks are
maintained, which will be consulted to extract results and raw data for
processing into graphs for research reports and published manuscripts.
The contractor is expected to perform all necessary data storage in
digital format as well. Records will be retained and reviewed by the
Section Chief.

e\) Data will be analyzed using appropriate statistical approaches to
demonstrate significant differences resulting from experimental
manipulations.

f\) The contractor must have a working knowledge of bioinformatics and
skilled in the use of database search programs related to DNA and
protein sequence analysis and manipulation. The person must be able to
use the information to design DNA cassettes for expression of fusion
proteins.

g\) The contractor should have excellent oral communication skills and
be able to independently write high-quality manuscripts for publication
in top tier journals.  

**Personnel, evaluation and schedule**

A. [Personnel]{.underline}

d\) The contractor must have a working knowledge of and experience in
signal transduction, gene regulation, molecular biology and disease
diagnostics. The contractor has advanced skills in molecular biological
methods such as generating mammalian and bacterial expression vectors,
mutagenesis, high-throughput cloning, cell biology, RNA extraction, cDNA
synthesis, polymerase chain reaction (PCR), cloning of DNA fragments and
cDNAs and subcloning into plasmids and various forms of differential
hybridization. The contractor shall have experience in microscopy using
immunofluorescene, and experience in protein/DNA sequence analysis and
bioinformatics. Personnel provided under the contract will comply with
the rules and policies of the NIDCR and its staff.

B. [Evaluation]{.underline}

The contractor is expected to work in an independent self-motivated
fashion. The contractor is expected to work closely with the Section
Chief and other members of the laboratory and will be evaluated at least
once a week, if not daily by the Section Chief. If the contractor is
considered to be substandard in the judgment of the supervisor, the
contractor will initially receive notice of the problem from the
supervisor and will be required to take corrective measures and to
demonstrate improved performance.

C. [Schedule]{.underline}

The contractor will perform studies for a minimum of 40 hours per week,
Monday through Friday (except any Federal holidays). Failure to arrive
on time or to follow the time schedules or instructions as indicated
shall be considered default of the contract.

D. [Reporting Requirements]{.underline}

The contractor shall provide professional services for Neurobiology and
Pain Therapeutics Section, NIDCR during the period of October 1, 2007 to
January 18, 2008. The contractor will be paid a total of \$43,632.00 for
this 4 month period.

Task Description: Dr. Peter Burbelo

Firm will issue 8 checks on the following days for the following
amounts:

October 12^th^ for \$5454.00

October 26^th^ for \$5454.00

November 9^th^ for \$5454.00

November 23^rd^ for \$5454.00

December 7^th^ for \$5454.00

December 21^st^ for \$5454.00

January 4^th^ for \$5454.00

January 18^th^ for \$5454.00

Checks will be issued to Peter Burbelo for payment as per diem and
travel expenses during his stay at NIDCR. It is estimated that Peter
Burbelo will arrive at NIDCR on October 1, 2007 and will depart on
January 18, 2008 a total of \$43,632.00 shall be paid in 8 payments. The
checks should be sent via express mail to the NIDCR, to the attention of
Cynthia Williams at the following address.

Cynthia Williams

Administrative Officer

National Institute of Health

National Institute of Dental and Craniofacial Research

30 Convent Drive Room 5A503

Bethesda, MD 20892

301-496-1483