Minor Research Project Organic Chemistry

2018-2019
Dit vak wordt in het Engels aangeboden. Omschrijvingen kunnen daardoor mogelijk alleen in het Engels worden weergegeven.

Doel vak

The aim is to obtain experience in scientific research including the
design and execution of experiments and to critically interpret and
reflect on the experimental results. The project will be conducted
within the field of “Synthetic Organic and peptide chemistry “or
“Structural chemical biology” in one of the following settings:
- University or Academic hospital
- Research institute
- Company
The internship can be performed either within the Netherlands or abroad.

Inhoud vak

The specific content of the project depends on the associated
supervisor(s), available projects on host/location and the timing of the
internship, but roughly deals with one of the following areas of
research:

- Organic small-molecule chemistry: development of efficient synthetic
methods for making biologically relevant molecules. The synthetic
toolbox that enables us to make small molecules for drug discovery is
never ‘complete’, yet continuously expanding. New and efficient
synthetic methods/routes are developed for making ‘drug-like’ compounds.
Starting from solid theoretical knowledge of organic chemistry, both new
multi-component- and cascade-reactions (in which in one step multiple
covalent bonds are formed) as well as new conversions using bio-,
organic or transition metal catalysis are applied. With such reactions,
multiple outcomes are often possible. Using advance spectroscopic
techniques, all products are characterized, and subsequently, the
reaction can be optimized to one specific product. The scope of the
reaction is determined after establishing the ideal conditions for the
newly developed reaction and molecular diversity is the primary driver
in choosing the products. Finally, to underline the utility of the newly
developed reaction, interesting applications are actively pursued.

- Organic and peptide chemistry: Ligands that selectively bind to
biomolecular targets are a prerequisite for most strategies aiming at
the elucidation or modulation of biological processes. The discovery of
these ligands can be very challenging. Giving the huge amount of
available structural data, known peptide binding epitopes provide a rich
source of inspiration for novel ligands. Preorganization of such
peptides into their bioactive conformation or the use of rigid
peptidomimetic scaffolds have been applied to ensure binding affinity
and bioactivity. Notably, there is a lack of approaches for the
stabilization of irregular and complex peptide structures. In addition,
the design of peptide-derived bioactive compounds is often hampered by
their low cellular uptake and biostability.
Addressing these challenges, the design of peptide-inspired ligands for
an application in proximity-induced chemical reactions and as inhibitors
of protein‒protein interactions is pursued. The core techniques applied
in corresponding projects include organic synthesis of non-natural amino
acids, solid-phase peptide synthesis and/or the biophysical validation
of ligand─receptor interactions (e.g. via fluorescence polarization
assays).

- Structural chemical biology: The interaction networks of biomolecules
such as nucleic acids or proteins are crucial for proper cell function.
Once imbalanced, a variety of severe diseases can be the result. Here,
we focus on key players of various cancers as well as their interaction
partners. We will explore their protein-protein- as well as their
protein-DNA complex formation and use small molecules as modifiers of
these interactions. We will also determine their interaction mechanisms
on atomic level and use this information to optimize the potency of the
small molecule modulator. A subset of the following techniques may be
used: sub-cloning genes of interest in suitable expression plasmids,
heterologously expressing these in bacteria and purifying them via
various chromatography techniques. The quality of the resulting proteins
will be analyzed using SDS-PAGE and mass spectrometry. With state of the
art crystallization techniques we will search for crystallizing
conditions and optimize crystal formation. Subsequent X-ray analysis and
structure determination will help to optimize small molecule modulators
of protein-protein interactions.

Attention will be paid to setting up new research/experiments, using
state-of-the-art experimental techniques, analyzing experimental results
and keeping adequate documentation.

Onderwijsvorm

Literature review, formulating a research question, conducting
experiments, keeping adequate documentation (e.g. lab journal),
analyzing data, reporting on results in progress/group meetings, in a
written thesis and final presentation within the research group.

Toetsvorm

Academic attitude, execution, oral presentation, and written thesis

Vereiste voorkennis

Entry requirements with respect to attained courses and number of
credits apply. See the Education and Examination regulations and the
internship manual Drug Discovery & Safety. For questions, consult the
internship coordinator well in advance (internships_sf.beta@vu.nl).

Literatuur

Starting literature will be provided by the supervisor. The first 1-2
weeks of the traineeship will be spent on literature reading and
preparation for the project.

Doelgroep

Research variant of all tracks within the master DDS

Overige informatie

The length of a minor internship ranges from 18 to 36 EC (3-6 months)
and can be (partly) incorporated within the optional part of the master
program, although for traineeships abroad and in companies a length of
at least 30 EC is recommended. Consult the master coordinator of your
track well in advance to discuss your personal education plan. See the
“Master Drug Discovery & Safety Internship manual” for more information
(rules, regulations, tips, etc.) on the internship process. This manual
can be found on the canvas community “Master Drug Discovery & Safety”.

Afwijkende intekenprocedure

The number of internal (VU) internship positions is limited. Candidates are selected based on their motivation letter and CV in an application procedure. See the canvas site “Master Drug Discovery & Safety” for more information regarding this application procedure. Be aware that selection procedures exist for most external positions as well. Before the start of the project an internship agreement has to be signed by all involved parties and the project proposal has to be approved by the VU supervisor. See the “Master Drug Discovery & Safety Internship manual” for more information on the rules and regulation regarding internships. If after reading the manual you still have questions regarding the process related to internships, admission, approval, etc., please contact the internship coordinator via internships_sf.beta@vu.nl.

Algemene informatie

Vakcode XM_0048
Studiepunten 30 EC
Periode Ac. Jaar (sept)
Vakniveau 500
Onderwijstaal Engels
Faculteit Faculteit der Bètawetenschappen
Vakcoördinator dr. D.J. Scholten
Examinator dr. D.J. Scholten
Docenten

Praktische informatie

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