Twycross Newsletter AutumnWinter 2021

Alumni update
Matthew Raybould
Matthew left Twycross House in 2012 to read Chemistry at Oxford (Merton).
After the taught portion of my
undergraduate Master’s in Chemistry
at Oxford, I decided to undertake a
project in computational chemistry
research (much to the relief of
laboratory scientists everywhere
— my practical skills were never
the best!). I enjoyed the challenge
of coding and data analytics but
wanted to apply the methods in a
more biochemical/drug discovery
context. This led me to starting a
DPhil (PhD) in “Systems Approaches
to Biomedical Sciences”, also at
Oxford (2016-2020).
I ended up specialising in antibody
research, under the supervision of
Professor Charlotte Deane in the
Oxford Protein Informatics Group
(OPIG). Antibodies are a fascinating
class of protein, since their highly
mutable (yet well-defined) shape
and chemistry allows them to bind
specifically to harmful targets
and mark them for eradication by
other proteins. The body therefore
produces millions of subtly different
antibodies at any one time, termed
an “antibody repertoire”, as a
defensive mechanism to fend off
pathogens. Individual antibodies
can also be deliberately engineered
in the laboratory to act as ultraspecific
drugs to tackle a huge range
of diseases.
Work in this field couples
intellectually stimulating problems
with clear biomedical applications.
A key publication from my DPhil
was a new tool (the Therapeutic
Antibody Profiler) that analyses
the biophysical properties of
an antibody surface to advise
pharmaceutical scientists when
an antibody drug candidate may
be tricky to manufacture and
formulate into a medicine. I also
developed a method which analyses
the diversity present in a healthy
human antibody repertoire and uses
this understanding to rationally
design more efficient “antibody
screening libraries”. These are initial
pools of candidate antibodies that
a pharmaceutical company can
probe against a new target in the
early stages of a drug discovery
campaign.
When COVID-19 hit back in
March 2020, I was well-placed
to contribute to the pandemic
response efforts. In May 2020, I
worked alongside colleagues at
Oxford, clinicians at Barts Hospital in
London, and scientists at Alchemab
and Illumina, to publish the first
analysis of the antibody repertoires
of UK patients responding to
SARS-CoV-2. We found distinct
molecular patterns indicating
that the repertoires of recovering
patients were responding in a similar
(“convergent”) manner, knowledge
that Alchemab and fellow start-up
Iontas later applied to produce a
COVID-19 therapeutic antibody.
Throughout the pandemic, I’ve also
curated the “Coronavirus Antibody
Database”, a repository of molecular
information of any antibody tested
under laboratory settings and
found to engage a protein on the
surface of any coronavirus. Now
comprising around 3,500 entries,
this has become one of the major
hubs of information for researchers
studying the immune response to
SARS-CoV-2. It has been accessed
by over 6,500 unique users in 85+
countries and was generously
recognised with an Impact Award
by Oxford University earlier this
year. The deluge of studies into
SARS-CoV-2 is now starting to
abate somewhat, but the experience
of working in such a dynamic and
intense environment is one I will
never forget.
After my DPhil ended, I decided
to stay in OPIG to conduct
postdoctoral research alongside
pharmaceutical company Boehringer
Ingelheim. My current project twins
antibody and T-cell receptor analysis
to improve our understanding of
how their biochemical properties
are linked to their bodily functions.
Ultimately, we hope this knowledge
can be translated in oncology drug
discovery, to develop tumourspecific
antibodies that mimic the
behaviour of T-cells.
I’ll always be grateful to the fantastic
teachers at Twycross House (Dr.
Brooks, Mr Pullen, Dr. Wharton, Mrs.
Cartlidge, Mrs. Van Arkel, and many
more besides!) who prepared me so
well for all the challenges I’ve faced
in this first stage of academic life.
I can’t wait to visit again one day,
when the circumstances allow!
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