►
Description
Open project meeting for Open Source Antibiotics Series 1, the Mur Ligases.
Full Project: https://github.com/opensourceantibiotics/murligase
Relevant GitHub Issue: https://github.com/opensourceantibiotics/murligase/issues/92
On the call: Dr Edwin Tse, Yuhang Wang, Yiwei Wang (UCL), Prof Chris Dowson (chair), Dr Adrian Lloyd and Dr Laura Diaz Saez (University of Warwick), Dr Joe Eyermann, Dr Lori Ferrins (Northeastern University), Bart Staker (SSGCID), Jan Abendroth (UCB Pharma).
A
A
Then
then,
so
the
problem
that
happened
was
the
room
was
at
high
temperature
for
four
or
five
days,
because
the
temperature
control
system
didn't
work,
so
it
was
reported
on
a
Thursday,
but
it
was
not
solved
until
Monday,
and
that
has
basically
done
that.
All
these
payments
that
I
had
done
didn't
work.
A
So
I
did
tested
some
of
the
crystals
at
Diamond
over
the
weekend,
but
I
didn't
have
enough
diffraction
from
them
from
the
crystals
that
kind
of
survived
and
anything
that
I
tried
for
soaking
in
terms
of
new
data
crystals
that
were
around
not
looking
great,
but
at
least
around
those
crystals
did
not
diffract
and
conquistiles.
Were
they
also
look
damaged,
but
they
go.
I
got
some
like
poor,
defractional,
Aid
accidents.
It's
still
not
good
enough
for
any
of
the
work
that
we
want
to
do
so.
A
I
need
to
repeat
these
experiments
in
the
next
weeks
and
the
next
data
collection
time
is
going
to
be
in
January,
so
I'm
aiming
for
the
first
weekday
open
at
Diamond
because
diamond
is,
will
be
closed
in
in
a
week
and
a
half
yeah.
So
that's
gonna
be
on
the
week
of
the
18th
of
January
18th.
They
will
be
open,
so
I
want
to
send
the
crystals
before
the
week
before.
So
we
get
the
first
days
of
data
collection.
A
A
So
and
crystallization
experiments
that
I
had
done
for
the
Heats
that
we
got
and
then
you
also
took
crystals
as
well
with
the
w
compound
sorry
Johan
compounds
in
this
round.
I
will
include
the
two
other.
The
additional
compounds
that
you
can
send
and
I
have
an
extra
extra
crystals
for
that,
but
yeah.
So
it
was
all
that.
B
Yeah,
that
was
that
was
that
was
sad.
We
have
a
really
nice
crystallography
room,
that's
very
temperature
controlled,
but
obviously
not
on
this
instance.
So
some
central
control
system
went
and
everything
got
lost.
I
think
it
goes
to
show
how
he
he
label
these
mirror
crystals
on.
Isn't
it
because
the
pvps.
A
A
Yeah,
so
it
was
seen
at
23,
I
think
on
Saturday,
which
would
have
been
okay
for
me
or
the
crystals,
not
for
me,
but
Mir
D
should
have
been
fine
but
I
think
over
the
weekend,
because
a
peep
is
out
seemed
to
be
as
well,
not
super
happy.
A
Maybe
it's
just
gone
much
harder
and
much
higher.
We
also
got
other
questions
for
all
their
targets
and
yeah
the
same.
So
with
another
specific
time
with
a
student
we
usually
used
to
have
1.8
1.5
hours
solution
and
the
maximum
we
manage
is
2.6.
So.
B
Yeah
so
we're
going
to
buy
a
separate
Standalone
incubator
to
go
inside
that
room,
there's
about
some
races
option,
but.
B
Any
other
structural
input
at
the
moment,
nope.
A
A
B
Great
lovely,
but
have
you
got
anything
from
your
end
structure,
wise
or.
C
No,
we
haven't,
we
talked
to
Joe
about
priorities
and
I
I'm,
but
we
haven't
done
any
actual
work
lately.
Besides,
we
did
get
all
the
structures
deposited
as
I,
think
John
reported
last
time
and
I
think
and
those
should
be
released
by
now
too,
but.
A
C
Yeah
well,
I
also
think
I'm,
not
even
sure
what
we
should
do
so
I,
don't
know
which
proteins
I
need
like
do
you
have
a
specific
request.
A
So
I'm
mainly
doing
Nikolai,
so
any
any
other
system
that
might
work.
If
you
have
the
protein,
if
not
acid,.
C
A
C
A
C
C
B
Cool,
oh
welcome.
My
dream
well
done.
B
All
right
should
we
move
on
to
the
essay
presentation
that
you've
got
then,
so
we
have
an
enamine
essay
update,
yeah.
D
Okay,
so
basically
we're
going
to
go
through
what
we've
been
doing
with
pseudom
minus
my
D,
the
Stockton
assay
thereof,
and
how
we've
actually
now
rolled
that
out
against
the
enemy
library
and
how
actually
we're
dealing
with
the
results
that
have
come
out
of
it.
D
So
to
remind
you,
all,
we've
got
and
I
say
that
basically
detects
phosphate
as
a
function
of
the
generation
of
uric,
acid,
wires,
antioxidase
and
PNP
that
generates
hydrogen
peroxide
and
essentially,
we've
used
that
as
a
continuous
assay.
But
we've
basically
worked
into
a
stopped
assay
where
essentially,
we
have
I'll
bring
it
on.
D
A
stopping
reagent
made
by
thermal
Fisher,
which
basically
stops
fluorescence
accumulation
via
the
eight
amplex
red,
and
we
have
basically
worked
that
into
a
stop
now
saying
that
from
a
pseudomonas
region,
asmrd
gives
good
linearity
with
respect
to
protein
decent
time
dependent
kinetics
of
fluorescence
accumulation,
which
gives
us
rough
linearity
up
to
about
20
minutes
with
a
nice
big
window
between
where
we
get
activity
in
the
presence
of
deglutamate
and
not
in
its
absence
and
with
reasonably
attractive
Z
Prime
parameters,
in
other
words,
the
statistic
that
allows
you
to
distinguish
between
what
is
and
isn't
enzyme
activity.
D
So
with
that
in
hand,
if
I
just
go
from
down
to
the
fourth
slide,
so
we've
now
have
that
and
it's
very
full,
well
format
and
essentially
I
can
just
go
to
300
Force.
D
The
way
we
go
about
business
now
is
that
we
have
in
the
first
Becky
button.
He
said
in
the
first
four
columns.
D
Basically,
we
have
controls,
so
the
enzyme
plus
DMSO
with
water,
the
enzyme
plus
DMSO
plus
deglutamate
the
same
in
this
in
in
columns
four
and
five
the
same
thing,
but
with
our
standard
inhibitor,
ADP,
CP
and
then
the
compounds
basically
are
mixed
together
without
the
deals
made
substrate
along
Wells
A6
to
a24
and
in
the
bottom
row,
06
to
o24,
and
then
quite
literally,
we
just
pipette
down
from
each
particular
submaster
mix
to
generate
a
triplicate
of
water
control
and
triplicate
of
the
activity
in
the
presence
of
deglutamate.
D
And
what
I'm
going
to
talk
about
essentially
is
plate
BO2,
although
we
have
done
the
other
half
of
the
enemy
Library
as
well,
but
over
the
eight
plates
that
cover
out
the
half
of
the
library
I've
done.
We
get
an
average
Z
Prime
of
that
0.66
calculated
from
Lanes
one
and
two
sorry
Lanes.
Two
and
three
is
as
I
have
it
here
and
we're
quite
happy
with
that
as
an
assay,
and
we
do
all
this
on
a
very
scan,
flash
Plate
Reader.
D
Although
this
is
in
some
ways
a
little
bit
meaningless,
but
essentially
it
just
demonstrates
the
point
we
have
over
the
302
compounds
in
plate
BO2
a
range
of
degrees
of
inhibition,
going
all
the
way
up
to
about
100
on
the
right
hand,
side,
and
if
we
triage
everything
and
have
a
cutoff
of
50,
we
have
26
compounds.
D
The
Red
Bar
corresponds
to
inhibition
by
ADP
CP,
but
those
26
compounds.
They
are
then
subject
to
further
analysis
because
they
may
well
inhibit
the
coupling
enzymes.
So
we've
developed
a
stopped
coupling
enzyme
assay
whereby
we
basically
take
pure
nucleus
like
bus
rollers.
We
give
it
0.1
millimole
of
phosphate
and
allow
it
to
generate
fluorescence.
D
D
Essentially,
the
results
are
that
if
we,
if
you
look
at
the
top,
the
bottom
two
graphs
bottom
left
is
what
we
see
when
we
carry
out
the
more
stringent
pnps
right.
So
there
are
some
seven
compounds
which
give
less
than
30
inhibition
in
the
coupling
enzyme
assay
but
gives
significant
inhibition
the
Murdy
assay
and
those
we
if
you
like,
have
in
the
bank.
D
If
we
do
the
less
stringent
variety,
something
like
19
compounds
get
through
as
compounds
of
interest,
and
we
basically
then
are
going
to
triage
those
with
a
further
PMP
I,
say
based
upon
a
different
principle
to
ensure
that
we
are
looking
at
murder
inhibition
but
of
the
seven
compounds
we're
absolutely
certain
about
complete
BO2
and
we'll
post
the
structures
on
the
website.
But
here
they
are,
we
have.
D
We
have
to
do
ic50s
on
these
things
to
see
exactly
what
their
potency
is
like
and
as
regards
plate
b01
using
the
more
stringent
screening
with
a
coupling
enzymes.
D
D
The
F7
we've
just
trialed
that
at
a
single
ATP
concentration,
so
we
don't
know
yet
exactly
what
it
is
competing
with,
and
that
really
is
the
state
of
play
at
the
moment.
So
it's
a
work
in
progress.
We've
got
to
basically
finish
the
coupling
enzyme
screen
and
finish
the
ic50s
and
then
see
where
we
go
from
there.
Then
that's
it.
B
D
But
like
I
say
we
also
have
a
variety
of
other
interesting
candidates
as
well.
D
E
Just
a
quick
question
from
from
me
sorry,
I'm,
I'm,
walking
around
so
I
on
a
small
screen,
I
couldn't
quite
see
the
the
detail
of
the
slides.
It
looks
very
interesting.
Does
that
change
any
of
the
previous
hits
that
we
have
brought
analogs
off
and
might
be
pursuing,
or
is
it
too
early
to
say.
D
It's
clearly
to
say,
because
yeah,
but
at
the
moment
that
those
pits
come
from
the
first
plate
and
I.
We
haven't
completely
finished
analysis
of
of
that.
Yet
so
it's
a
little
too
early
to
say.
C
D
I
would
imagine
that
we
would
have
all
the
coupling
enzyme
screening
done
by
Christmas.
I
would
imagine
we
would
have
depending
upon
how
many
ic50s
we
do
wind
up
doing.
We
will
probably
have
that
finished.
I
would
imagine
by
first
second
week
of
January.
B
And
Anita
who's
not
well
today
and
not
on
the
call
has
been
investigating
setting
up
those
assays
on
a
robotic
system
that
we
have
in
the
department
elsewhere
and
I
think
the
plan
would
be
to
set
up
the
Muir
D
E
coli
assay
to
screen
against
all
of
the
compounds
as
soon
as
we
get
back
in
January
I.
Think
that's!
That's
the
plan.
If
we
have
the
reagents
in
hand.
D
Well,
we
should
do
yeah,
I
mean
and-
and
certainly
if,
if
the
robotic
side
of
it
works
out,
then
it
also
makes
rolling
out
the
enemy
library
to
the
other.
Ligas
is
far
less
that
were
daunting.
Prospect,
perhaps.
B
Yes,
so
so
I
think
we're
going
to
be
able
to
cut
down
the
experimental
time
quite
significantly
using
using
that
which
means,
rather
than
just
having
to
cherry
pick,
hits
and
move
even
from
one
language
to
another.
We
can
at
least
for
a
few
of
them,
re
repeat
the
whole
Library
wow
I.
D
Think
like
and
then
the
manual
method
we
use
to
do
it.
We
basically
did
it
in
maybe
three
people
doing
it,
but
it
took
us
around
about
what
three
four
days
in
total
and
the
actual.
In
actual
fact,
although
you
think
has
stopped
us
saying,
makes
things
easier
and
in
some
ways
it
does,
it
still
took
us
something
like
another,
three
or
four
days
to
actually
get
to
the
stage
where
we
knew
or
had
some
idea
of
what
was
what,
in
terms
of
inhibition,
simply
through
the
numbers.
Okay,.
E
Just
a
quick
question
when
you
say
complete
the
the
screen:
do
you
mean
of
the
the
600
member
enamine
Library.
D
So
at
the
moment,
what
is
incomplete
is
the
coupling
enzyme
triage
that
we
do
to
ensure
that
what
we're
looking
at
is
specific
Modi.
D
So,
although
that
is
complete
for
BO2,
it's
not
complete
for
bo1
the
the
other
enemy
in
place,
so
that
still
has
to
be
done
and
then,
depending
on
what
your
definition
of
completion
is
and
mine
will
be
ic50s,
and
ideally
some
idea
of
what
is
being
targeted
in
terms
of
a
site.
Then
essentially,
I
would
like
to
think
we're
done
when
we
get
to
the
stage
where
we
know
or
have
a
collection
of
current
bands
which
are
genuinely
ATP
competitive
foreign.
E
Okay,
that's
fantastic,
and-
and
there
was
one
more
question
apologize
if
you
covered
this
already
previously,
you
were
talking
about
compounds
that
appeared
to
be
interfering
with
the
assay
I'm,
assuming
that
yeah,
if
you
have
you
gotten
rid
of
those
compounds
or
or
is
that
still
an
issue
with
the
assay?
No.
D
I
mean
we,
we
know
what
they
are
so
certainly
with
the
the
enemy
Library
I
mean
the
enemy.
Library
is
interesting
because
the
number
of
non-specific
heads
we're
getting
does
vary
depending
on
which
place
you
looking
at
look
at,
and
that
probably
is
also
a
function
of
the
way
the
Plate's
constructed,
which
Joe
would
probably
know
more
about
than
I
do.
But
but
the
thing
is
that
that
we
we
even
even
though
we
do
have
some
things
which
do
inhibit
non-specifically.
D
We
are
probably
getting
anything
up
to
about
19
compounds
out
of
300
that
are
of
interest
that
give
greater
than
50
inhibition,
and
if
the
coupling
enzymeciates
work
out
in
the
way
I
think
they
will
do,
they
will
also
turn
out
to
be
Murdy
specific
molecules,
although
I
have
to
do
the
experiment.
First,
if
that
answers
the
question.
E
B
Adrian
I
think
it'll
be
more
question
of
how
how
we
rationally
try
to
prioritize,
which
which
series
to
work
with
so
I
think
I
think
you
know
early
in
the
New
Year.
We
need
to
sit
down
with
all
of
the
data
with
all
the
chemotypes
and
all
the
different
you
know
hit
series
or
or
Singletons
or
whatever,
once
we've
got
all
that
together
and
just
have
a
rational
long,
a
long
hard
look
at
it.
Yeah
that'll
be
the
key
thing
as
to
what
to
progress.
Next.
E
Yeah
absolutely-
and
you
know,
Ed
has
already
ordered
a
huge
variance
of
some
of
those
schema
types,
but
but
yes,
I
mean
well
that
that
won't
be
all
of
them,
so
we'll
have
a
little
bit
of
information
on
some
of
them,
but
but
absolutely
not
all
of
them.
Yeah
yeah.
D
D
If
there's
any
way
of
actually
mining
that
fat
structurally,
it's
it's
rather
like
trying
to
work
out
why
things
don't
work
as
opposed
to
why
they
do
it's
as
to
why
there's
anything
special
about
the
compounds
that
basically
allows
them
to
discriminate
between
the
four
enzymes
involved,
in
other
words,
that
muddy
there's
anything
Ox
stays
the
PMP
and
the
hrp
foreign.
E
Well,
certainly,
it
would
be
interesting
to
see
if
they
have
any
any
particular
bit.
You
know,
I,
don't
know
risky
bit
in
in
the
structure
which
might
account
for
the
interference
yeah
I
mean
if
they
share
a
chemotype,
yeah
yeah
inspect
by
eye.
B
Yeah,
so
what
we
will
do
is.
D
B
Taking
taking
these
19
or
so
hits
and
then
was
in
them
through
other
ligase
assays
as
well,
so
you
know
see
see
in
pseudomonas
c
and
e
and
e
coli,
CD
and
E.
You
know,
while
we're
waiting
for
the
whole
the
whole
enemy
library
to
be
run
again
on
on
miod
just
to
see
which
of
these
are
fairly
mere
ligase,
promiscuous
I.
Guess
we're
wanting
to
go
to
a
point
where
we
can
identify.
You
know
a
good
number
of
those
and
and
then
even
even
early
on.
E
D
One
last
thing:
we
need
to
revisit
life
Arc
and
also
the
competition
compounds
as
well,
which
we
haven't
had
the
time
to
do
yet,
but
we
basically
need
to
sort
out
another
assay
for
those
they
are.
They
have
been
left
behind
slightly
and
they
need
to
be
done.
But
I
need
to
look
into
that.
D
B
Yeah,
let's
just
going
back
I,
can't
remember
how
I
oh
yeah.
It
was
David
schlay
Joe
when
I
was
talking
to
him
last
week,
when
he's
also
done
mirror
enzymes
and
I.
Think
all
of
all
of
their
efforts
ended
up
with
a
lot
of
toxic
compounds.
From
his
experience.
B
Yeah
yeah,
yeah
and
yeah,
and
and
GSK
just
spent
20
30
years
re-engineering,
their
latest
UTI
componential
support,
spent
all
that
time
trying
to
get
the
toxicity
out
of
it,
so
yeah
yeah
it
is
doable
retrospectively
but
prefer
not
to,
but
anyway,
those
two
you've
got
a
couple.
You've
got
seem
to
be
nice
and
clean,
at
least
in
the
enzymes
we've
got
so.
D
D
We've
got
a
total
of
19,
the
resident
residue
of
which,
in
other
words,
12
probably
needs
another
coupling
enzyme
and
another
no
lie
guys.
I,
say
just
to
ensure
that
they
are
working
in
the
way
I
think
they
are
and,
like
I
say
we
should
have
enough
compounds
to
make
deductions
from.
B
And
and
as
soon
as
Laura's
got
a
crystals
back
up
and
running
again,
we
get
those
as
many
of
those
that
are
amenable
to
going
in
Hope
Police
structures.
So
yeah.
A
B
A
I've
got
I
did
brought
in
already
before
leaving
so
the
protein
should
be.
Okay,
I
just
don't
know
how
much
money
peptide
is
left,
but.
B
B
E
The
those
the
fragments
are
sorry
they
you
see,
you've
got
me,
you
got
me
doing
it
now,
they're,
not
really
fragments
I,
don't
think,
though,
so
aren't
they
molecular
weight
like
plus
300,
just
in
the
terminology
of
it,
they're
sort
of
elaborated
fragments,
and
just
the
fragment
to
me
means
pretty
pretty
small
like
a
couple
of
rings.
With
some
of
these
enamine
compounds
and
Aston
White's
compounds
are
quite
they're,
quite
big.
B
We
ought
to
start
thinking
about
where
we
want
to
go
to
for
money,
to
press
on
further
and
and
drawing
up
a
series
of
criteria
as
to
as
to
where
we
need
to
think
we
need
to
get
to,
and
if
that's,
if
that
is
antimicrobial
activity,
that's
that's!
That's
definitely
one
thing
so
we'll
probably
need
to
have
a
kind
of
a
a
kind
of
a
sense
check
as
to
how
much
fuel
we
have
in
the
tank
to
keep
the
chemistry
going.
B
We're
we're
fortunate
at
Warwick.
We've
got
that
lump
of
money
to
keep
Adrian
and
Anita
and
Julie
gang
for
a
while
and
Laura,
but
they've
got
other
things
to
do
as
well
in
life
rather
than
just
this
and
it'd
be
nice
to
get
some.
You
know
funding
to
get
some
dedicated
staff
on
this,
so
they
can
go
off
and
have
another
life
in
another
world
of
science
as
well
as
real
ligazers,
so
it'd
be
good
to
to
Think
Through.
B
What
we'd
like
where
we'd
like
to
get
to
Joe?
Do
you
have
any
thoughts
about
NIH
and
what
you'd
like
to
get
to
on
the
U.S
side.
E
There
was
the
CC
carb
funding.
Right,
which
is
is
a
is
a
well
normally
a
us-based
thing.
If,
if
you
get
to
something
which
has
some
SAR
seems
like
it
might
be
promising
as
an
interim,
but
but
certainly
from
our
perspective
yeah,
we
you
hangs
doing
a
PhD
in
the
e-way
is
doing
an
an
amress,
and
but
besides
that,
you
know
we're
gonna
we're
our
our
antibiotics.
Research,
UK
Grant
ends
in
January,
so
yeah
we're
gonna
need
something.
B
So
practically
you
know
if
we,
even
if
we
wrote
something
in
and
submitted
it
in,
you
know
you
know
well.
C
B
Can't
I
don't
think
we
could
submit
anything
in
January
because
I
don't
think
we
have
enough
data
necessarily
unless
there's
some
super
super
early
option
to
go.
For
you
know
we
we
probably
need
to
to
find
enough
money
for
the
next
six
to
nine
months,
maybe
even
a
bit
longer.
Perhaps
unless
we
can
get
some
to
get
a
big
Grant,
you
know
we'll
we'll
need
definitely
that
length
of
money,
so
we're
gonna
have
to
find
some
more
interim
money
for
chemistry.
B
I'll
have
a
chat
to
Laurie
as
well
Joe
just
to
see
what
her
thoughts
are
on
on
that
side
of
things,
but
Matt
on
on
your
side
watch.
You
know
you
know
to
get
through
another.
You
know
you
know
half
half
dozen
or
so
or
a
dozen
or
so
additional
bits
of
chemistry.
What
what's?
What's
that
going
to
take
yeah.
E
There
is
a
there
is
a
UCL
scheme
called
the
therapeutic
acceleration
scheme
which
comes
out
twice
a
year
and
there's
around
in
January,
but
I
think
it's
focused
on
rare
diseases
if
memory
serves,
but
that
that
is
something
which
can
be
used
as
a
kind
of
bridging
scheme.
If
you
have
something
promising
or
need
it
progressed
slightly,
I
could
look
into
that.
E
Otherwise,
I
mean
I
think
that
if
some
of
these
molecules
are
hitting-
and
if
some
of
them
are
it
can
be
explored
with
commercial
sources.
So
if
we
can
develop
some
SAR
by
catalog,
you
know
by
ordering
a
bunch
of
reading
Bean
compounds,
then
it
is
in
a
sense,
a
little
simpler
because,
for
you
know,
sort
of
100
pounds
a
shot.
E
You
can
get
another
data
point
and
you
don't
need
to
pay
someone
to
do
it,
but
you
are
then-
and
you
see
you
can
generate
that
quite
quickly,
but
you
are
then
Limited
in
in
what
you
can
order,
because
as
soon
as
you
come
off
the
catalog,
then
it
gets
expensive.
E
So
you
know
in
in
the
short
term
to
bolster
SAR
it.
It
could
be
that
we
just
request
some
money
for
for
sort
of
commercial
synthesis
in
in
the
end
interim,
but
that
will
only
take
us
so
far.
C
F
Well,
I
mean
I,
I
I
have
no
standing.
Basically,
so
you
know
if
you're
gonna
get
funding,
I
mean
Lori
is
associated
directly
with
Northeastern,
so
I
have
no
standing,
so
it's
really
I
mean
Laura.
You
know
if
you're
going
to
try
to
go
after
any
U.S
funding,
whether
you
know
it's,
you
Lori
and
you
Bart
I
mean
who
needs
to
to
do.
You
know
any
kind
of
grant,
writing
and
and
and
solicitation
of
funds.
F
I
mean
I
I'm
I'm
here
to
assist
like
I,
have
been
for
the
last
four
plus
years,
but
I
don't
I'm,
not
you
know
she
talked
about
before
you
know
like
with
the
paper
and
everything
else
I
mean.
Basically,
you
know
someone
who
has
standing
I
guess
you
know
associated
with
University
needs
to
take
the
lead
on
that.
F
F
I
can't
do
anything
with
with
that,
for
you
guys,
you
know
if
you
want
help
somewhere
along
the
way,
I'm
willing
to
help,
but
I
mean
those
kind
of
decisions
and
how
you're
going
to
move
forward
in
that
aspect
of
Grants
and
papers
and
so
on.
You
need
to
kind
of
figure
that
out
and
he's
going
to
take
the
lead
and
how
you
want
to
approach
it.
C
Right,
I,
I,
agree
and
so
I
think
that
that's
what
we're
trying
to
do
is
is
figure
out
the
landscape.
My
my
opinion
on
NIH
funding
is
you
know
you
that
we
should.
We
should
have
an
application.
It
was
a
cycle
every
four
months
and
we
should
probably
start
probably
should
have
in
the
past
already
started.
Having
applications
in
every
cycle
is
r21s.
C
Did
you
don't
have
to
have
a
publication,
I
think
to
get
an
r21,
but
it
sure
helps
and
you're
not
going
to
get
an
r01
like
this
and
I.
Don't
think
we're
going
to
get
carb
funding
and
either
until
you
have
a
lead
molecule,
but
no.
C
So
but
I
do
so,
the
next
round
is
February
4th
and
then
and
also
the
problem
is,
you
know
it
takes
nine
months
to
get
any
funding.
So
the
next
application
deadline
is
February,
and
so
it's
not
short
term.
It's
a
mid
to
long
term,
but
it's
got
a.
C
We
have
to
start
submitting
applications
so
an
application
that
would
originate
for
me
and
I
I
have
got
r21s
and
I
have
an
r01
on
a
different
topic,
so
it
can
sponsor
from
here,
but
it
would
need
to
be
something
focused
on
what
we've
done
here
and
you
know
the
work,
the
structures
that
yawn
and
the
other
ssgcid
groups
did
so
I'm
happy
to
start,
brainstorming
that
and
figure
out
how
it's
not
a
ton
of
money
right.
It's
one,
one,
the
two
years,
275
dollars
over
two
years.
C
Well,
so
ssgcid
isn't
a
body
that
can
request
grants
or
it's
just
just
a.
It-
is
a
contract
by
NIH,
but
I
work
for
Seattle
Children's,
Research,
Institute
and
I
write
grants
for
Seattle,
Children's,
Research
Institute.
B
C
C
So
we'd
want
to
the
money
that
would
go
to
Seattle.
Children's
would
have
to
not
would
be
stuff.
That
would
be
in
addition
to
ssgcid,
and
then
ssgcid
would
write
a
letter
of
support
for
the
collaboration,
and
then
you
have
a
sub-award
that
would
go
to
one
of
the
you
know
the
other
labs
or
both
the
labs
there's
just
it's
a
small
plot
of
money.
So
we'd
want
to
make
it.
F
A
C
A
forget
the
name
but
the
primary
yeah.
F
I
understand
I've
been
on
multiple
NIH
grants
with
at
Northeastern.
We
have
like
three
grants
so
I'm
associated
with
it's
a
challenge.
You've
got
you've
got
to
work
through
is
as
as,
if
you're
going
to
do,
an
r21,
which
is
probably
you
know,
is
the
only
route
in
terms
of
NIH
funding.
At
this
point,
given
the
data
you
have
in
hand,
you
know
is
the
chemistry
chemistry
is
not
cheap.
You
know,
biology
is
even
more
expensive,
but
chemistry
is
not
cheap,
so
you
know
a
a
postdoc.
F
You
know
getting
a
postdoc,
for
example
at
Northeastern
you're
talking
about
at
least
like
probably
with
overhead
and
everything,
that's
like
70
or
80
000
a
year.
So
when
you
have
I,
think
it's
a
275
000
budget
right,
so
just
that's
where
you
guys
have
to
work
out.
You
know
in
terms
of
budgets,
you
know
it's
a
very
small
budget
and
you
know
how
you
want
to
how
you're
going
to
work
through
that
in
terms
of
the
nihr
21s
and
that's
at
least
in
the
US.
F
Even
with
the
data
you
have
in
hand,
I
think
you
can
probably
make
an
argument
for
an
r21
if
you
want
to
do
chemistry,
but
that's
probably
like
one
post,
that's
kind
of
one
post
lock
and
then
maybe
maybe
you
get
a
grad
student
or
something
at
in
in
Lori
and
Mike
plastery's
lab.
That
would
be
kind
of
the
thing
or
you
know.
Maybe
you
know
Matt.
You
can
talk
about.
You
know.
What's
your
Chemistry,
you
know
what
kind
of
what
the
options
would
be.
F
If
you
want
to
do
the
chemistry
you
know
at
UCL
and
again,
I
guess
the
question
there
becomes.
You
know
just
in
terms
of
how
NIH
looks
at
that,
you
know.
Do
they
want
to
the
fund.
You
know
on
r21
with
chemistry
and
at
UCLA
I,
don't
I,
don't
know,
I,
don't
know
what
the
odds
are
or
what
what
the
issues
or
if
any,
there
might
not
be
any
issue
to
do
that.
But
that's
where
you
guys
have
to
work.
You
know
talk
with
Laurie
and
you
guys
get
your
heads
together
and
decide.
F
You
know
how
you
want
to
if
you're
you
know
going
after
an
r21
at
this
point.
You
know
how
you
want
to
do
that.
That's
that's
one
option
and
then
the
rest
of
it
I
guess
you
got
to
figure
out.
What's
the
UK
EU
options
for
funding.
C
I
was
gonna
say
for
the
r21s
and
for
this
idea
I,
it's
similar
structure
as
this
would
probably
need
to
be
structured.
C
I
have
got
an
r21
where
it's
basically
two-thirds
of
the
money
goes
to
the
chemistry
lab
to
do
the
chemists
stuff
and
that
that
was
with
the
University
of
Washington
and
then
recently
we
submitted
another
one
that
had
a
international
collaboration
in
Sweden,
and
that
was
about
I
would
say.
Maybe
maybe
50
of
the
money
actually
went
to
Sweden
as
a
foreign.
You
know
entity
like
in
the
similar
Arrangement
like
this
and
we
didn't
get
funded,
but
that
that
was
never
a
criticism.
That
structure
was
never
the
CR,
wasn't
the
criticism
of
it.
B
I'm
just
wondering
with
the
chemistry
and
there's
a
question
is
the
chemists.
You
know
how
much
more
cost
effective.
Is
it
just
to
contract
synthesis
synthesized
compounds
you
know,
rather
than
going
through
all
the
university
overhead
of
a
pdra,
whether
you
just
say
all
of
that
money
goes
to
Wishy
or
someone
to
make
up.
10
compounds
or
20
compounds
is
either.
Is
that.
E
I
think
it's
a
it's
a
very
effective
bit
to
do
right,
so
I
think
in
any
chemistry
plan
you
have.
You
definitely
have
some
of
that,
because
there
are
times
when
that's
very
efficient,
but
there
are
times
when
it
isn't
necessarily-
and
of
course
you
know
what
you
hope
is
that
the
chemists
who
are
doing
the
lab
work
are
also
intellectually
contributing
to
the
project
which
you
know
is
certainly
helpful.
E
F
B
F
Experience
with
with
contracts,
and
so
at
wushy
Sinjin
is
that
you
know
the
FTE
cost
is
about
the
same
as
a
postdoc
in
the
U.S
which
again
you're,
you
know,
you're
talking
60
or
70
thousand
dollars
for
an
FTE
per
year,
and
and
then
you
know,
then
it's
a
matter
of
you
know
working
up.
You
know
how
many
you
know
the
challenge
you
end
up
with.
Is
you
know
once
you
have
your
lead
matter,
you
pick
out
decide
what
you
know
what
series,
what
what?
F
What
hits
out
of
the
let's
have
a
library
light
barking.
You
mean
Adam,
wise.
Whatever
then
you've
got,
you
know
how
many
you've
got
to
develop
the
chemistry
and
how
many
series
you
know
you
want
to
work
on
and
so
on.
So
it's
just
you
kind
of
go.
You
know
well,
obviously,
got
to
have
a
lot
more
discussion
and
kind
of
see
what
you
know.
Chemical
Equity
you
have,
and
then
you
know
what's
the,
but
it
might
accept.
F
My
experience
typically
with
cross
is
you're
talking
most
in
most
cases,
you're
talking
minimum
of
a
thousand
dollars
per
compound.
If
you're
getting
it
made,
someplace
else
I
mean
that's
like
an
individual
compounding
where,
obviously,
if
you
start
working
on
a
series
and
you've
got
Advanced
intermediates-
and
maybe
you
know
you
get,
you
get
a
few
more
compounds.
But
if
you're
talking
like
one-off
compounds,
typically
a
thousand
dollars
a
compound
for
getting
us
at
least
I-
think
at
a
sense
of
size
in
a
cro.
B
I
mean
the
reason
I
was
suggesting.
That
was,
it
might
be
a
way
for
the
us.
If
the
U.S
funders
didn't
really
want
to
pay
for
a
British
chemist
that
you
could
just
buy,
the
you
know
effectively
buy,
but
you
know
most
of
the
money
goes
to
just
to
buy
into
chemistry
and
yeah.
That
would
just
it
was
that
that
was
my
thought
on
that.
If
there
was
you.
F
Know
yeah
I
think
in
the
short
term,
what
I
would
suggest
is
kind
of
what
Matt
brought
up
earlier,
which
is
the
CCR
I
forget
the
hell,
the
acronym,
but
basically
this
NIH
program
that
they
will
provide
chemistry
to
follow
up
so
I
think
if
you
can
put
a
package
together
with
some
of
the
hits,
and
ideally
sorry
Laura.
But
if
you
had
a
crystal
structure,
then
I
think
you
can
make
a
pretty
strong
proposal,
maybe
to
the
NIH.
Just
this
chemistry
part.
That's
doing
you
know
it's
willing
to
to
make
compounds.
F
I
think
that
that's
definitely
something
that
the
team
should
pursue,
especially
in
the
near
term.
Again,
if
you
can
get
you
know
once
once
you
have
some.
F
More
data
nailed
down
in
Adrian's
lab
and
then
you
can
come
up
with
a
chemistry
plan.
I
I
would
I
would
put
that
kind
of
thing
forward
and
maybe
Matt
Matt.
If
you
want
to
leave
that
I
mean
you
know
whatever
again,
that's
just
how
how
I'm
sorry
I
I
just
don't
know
how
this
all
works
with
between
you
know,
NIH.
Definitely,
funds
I
mean
we
have
grants
right
now
with
between
Northeastern
and
Brazil
Northeastern,
South,
Africa,
Northeastern
and
Spain.
Okay,
these
are
all
NIH
r01
grants,
but
they're
all
looked
at.
F
F
The
one
with
Spain
is
more,
the
chemistry
is
being
done
in
northeastern
and
the
biology
there's
special
biology,
that's
being
done
in
Spain,
you
know
just
can't
you
know
can't
be
done
in
northeastern.
So
again
it's
just
these
are
things
again
talking
with
Laurie.
Maybe
she'll
have
a
better
sense
than
Matt
I.
Guess
your
colleagues
and
how
that
really
works
with
I'm
trying
to
get
you
know
connected
with
the
NIH
I.
Just
don't
know
how
that
I
mean
I'm.
F
E
Yeah
yeah
I
think
I
think
that
Chris
and
I
have
options
with
the
with
the
MRC
over
in
the
UK.
No
question
so
I
think
that
that
that
it's
not
as
if
there
isn't
an
option
there
I
think
that's
fine.
I
I
will
look
at
what's
required
for
the
cc4
carb
thing
for
chemistry,
I'll
I'll
find
out
what
the
application
process
involves
and
get
back
to
everybody
about
that,
but
I.
That
could
be
a
good
way
of
dealing
with
things
just
for
2023.
F
Yeah
yeah
I
mean
I
I
I
have
a
former
African
colleague
who
is
involved
with
that
at
the
NIH,
but
if
you
need
any
help
with
that,
Matt
I
mean
but
I
think
it's
good
for
you
to
take
the
you
know
you
can
take
the
lead
or
maybe
talk
with
Lori
or.
However,
you
guys
want
to
do
that
in
terms
of
pursuing
that.
But
I
think
that
should
be
a
priority
for
the
for
the
team.
B
B
Good
lovely
I'm,
not
following
the
agenda:
I'm,
sorry,
Matt,
I'm,
just
picking
up
extend
stuff.
Does
someone
have
something
else
they'd
like
to
specifically
cover.
E
Sorry
to
land
you
in
the
chair,
Royal
Chris,
no,
nothing
from
me.
Apart
from
all
this
stuff,
that's
on
the
on
the
page.
There
nothing.
E
Guess
the
one
thing
I
wanted
to
highlight
was
that
you
hangs
amine
the
amino
derivative
of
the
astrogenica
compound
AZ
5595
is
the
one
that
he's
sent
now
and
we
we're
just
very
excited
to
see
if,
if
the
data
on
that
look
good,
so
it
bound
nicely
on
SBR
I
guess
we're
just
gagging
to
see
if
it
inhibits
Mercy.
Yes,.
B
B
I
mean
it's:
data
sets
I,
think
next
time
we'll
be
able
to
present
the
SBR
versus
the
assays
and
actually
show
how
important
it
is
to
have
the
assays.
A
And
yeah
the
Johann
compounds
we're
also
going
to
do
the
mic's
right
yeah.
B
A
E
A
E
And
and
if
if
it
inhibits
the
enzyme,
then
it
might
be
one
to
try
on
the
on
the
bacteria
to
see
if
we
we
get
any
luck.
Yeah.
G
Yeah,
it's
just
just
have
a
question
before
we
finish
see
is
that
is
that
okay,
like
I,
dissolved
my
compounds
in
the
MSO
and
ship
it
like
this
time.
I
mean
the
concentration
was
around
10
milligrams
per
ml.
Is
that
okay,
this
time
like.
A
G
I
ship
it
like
a
15
milligrams,
each
compound
in
1.5,
mil,
that's,
that's
a
that's!
That's
the
concentration,
I
get
and
I
think
store
in
the
MSO
is
safe
to
yeah.
B
Cool
any
any
any
other
bearing
points
I'm.
Sorry
I
haven't
gone
through
ticking
off
all
of
the
to-do's
not
to
Do's,
but
I'm
gonna
have
to
go
at
three
anyway.
Yeah
same.
B
Yeah
great,
if,
if
not,
then
thank
you
all
for
joining.
Thank
you
for
the
data
those
who've
presented
today.
Thank
you
for
your
ongoing
chemistry,
Yan
and
everyone
else's
support.
Uk
and
us
I
think
we're
going
to
be
in
a
good
position.
Come
the
new
year
to
make
some
a
real
step
forward.
B
Once
we've
got
all
this
data
assembled,
so
I
think
that's
it's
looking
really
encouraging,
so
good,
nothing
else
to
say,
but
Happy
Christmas,
everybody
Matt
beat
me
to
it
with
a
chat
well
done
and
we'll
catch
up
in
the
New.
Year
that'll
be
excellent
and
any
any
any
breaking
news
before
their
new
one
about
your
compounds,
we'll
we'll
send
them
to
you
as
an
early
Christmas
present.